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A convenient approach to the synthesis of 2-(2-aminoethyl)pyrroles and their heterocyclization into hydrogenated pyrrolopyridines and related pyrroloindolizines

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A convenient approach to the synthesis of 2-(2-aminoethyl)pyrroles and their heterocyclization into hydrogenated pyrrolopyridines and related pyrroloindolizines
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  A convenient approach to the synthesis of 2-(2-aminoethyl)pyrroles and their heterocyclization intohydrogenated pyrrolopyridines and related pyrroloindolizines Marina V. Raiman, a Aleksei V. Pukin, a Vladimir I. Tyvorskii, a Norbert De Kimpe b and Oleg G. Kulinkovich a, * a  Department of Organic Chemistry, Belarusian State University, Fr. Scorina Avenue, 4, 220050 Minsk, Belarus b  Department of Organic Chemistry, Faculty of Agricultural and Applied Biological Sciences, Ghent University, Coupure Links 653, B-9000 Ghent, Belgium Received 17 January 2003; revised 15 April 2003; accepted 16 May 2003 Abstract —2-(2-Aminoethyl)pyrroles and 2-(2-succinimidoethyl)pyrroles were prepared from acetals of ethyl 4-oxoalkanoates via latentvinyl 1,4-dicarbonyl compounds as the key intermediates. The Pictet–Spengler condensation of 2-(2-aminoethyl)pyrroles with aromaticaldehydes gave 4,5,6,7-tetrahydro-1  H  -pyrrolo[3,2- c ]pyridines in good yields. 4,5,7,8,9,9a-Hexahydro-3  H  -pyrrolo[2,3- g ]indolizines wereprepared in a similar way starting from 2-(2-succinimidoethyl)pyrroles. q 2003 Elsevier Science Ltd. All rights reserved. 1. Introduction Pyrrolopyridines with different types of ring fusions andtheir partially hydrogenated derivatives are of great interestas aza-analogues of indole. 1 Methods for the synthesis of 4,5,6,7-tetrahydropyrrolo[3,2- c ]pyridines, which showinteresting biological activity and which have foundapplication as synthetic building blocks, were summarizedin a recent review. 2 The most important of them are basedon the pyrrole annelation onto the corresponding piperidin-4-one framework, as well as on the formation of ahydrogenated pyridine ring by means of cyclisation of 2-(2-aminoethyl)pyrroles. 3,4 The latter approach appearedto be effective in the synthesis of previously unknownoctahydropyridopyrrolopyridines in the acid-catalysedPictet–Spengler reaction. 5 Similar non-catalytic hetero-cyclisations have been also accomplished in the series of tryptamine derivatives and have preparative importance foracidophobic pyrrole and indole systems. 6,7 In the present work a convenient approach to the synthesisof 2-(2-aminoethyl)pyrroles  7a – c  and their succinimideanalogues  7d – f  , starting from carbonyl-protected esters of  g -oxocarboxylic acids  1a , b , is demonstrated (Schemes 1 and2).Thekeyprecursorsofcompounds 7 were b -bromoketones 4 ,  5  prepared by cyclopropanation of esters  1  with ethyl-magnesium bromide in the presence of titanium(IV) iso-propoxide 8 followedbybrominativeringopeningofthethree-membered ring in cyclopropanols  2a , b . 9 Compounds  7a – c were smoothly converted into 4,5,6,7-tetrahydro-1  H  -pyrrolo[3,2- c ]pyridines  10a – i  by reaction with aromaticaldehydes in  i -PrOH (Scheme 3). The related tricycliccompounds  13a – c , bearing the pharmacophoric indolizinefragment were accessible similarly from compounds  7d – f  (Scheme 4). 10 Herein we describe our results. 2. Results and discussion 6-Bromo-4-oxohexanal  4a  was obtained in three preparativesteps in an overall yield of 67% starting from ethyl 4,4-diethoxybutanoate  1a  via the cyclopropanol intermediate  2a as a key product (Scheme 1). Deprotection of aldehydegroup was performed after bromination of the substitutedcyclopropanol  2a , since hydrolysis of the latter led to theformation of the cyclic acetal  6 11 which was stable underbromination conditions. In contrast, deprotection of theketone group in cyclopropanol derivative  2b  proceeded withformation of monocyclic acetonylmethylcyclopropanol  3 , 8e and bromination of the latter led to 7-bromoheptan-2,5-dione  4b  in good yield (Scheme 1). The resulting b -bromoketones  4a , b  and  5a , b  were not stable and readilylost hydrogen bromide, merely upon contact with aadsorbent for chromatography. Therefore, these compoundswere used for further transformations without purification(purity . 98%;  1 H NMR spectroscopy). 0040–4020/03/$ - see front matter q 2003 Elsevier Science Ltd. All rights reserved.doi:10.1016/S0040-4020(03)00777-4Tetrahedron 59 (2003) 5265–5272* Corresponding author. Tel.:  þ 375-17-2095190; fax:  þ 375-17-2265609;e-mail: kulinkovich@bsu.by Keywords : cyclopropanols; 2-aminoethylpyrroles; pyrrolopyridines;pyrroloindolizines; Pictet–Spengler reaction.  Scheme 1.Scheme 2.  M. V. Raiman et al. / Tetrahedron 59 (2003) 5265–5272 5266  7-Bromoheptan-2,5-dione  4b  and 6-bromo-4-oxohexanal 4a  reacted readily with three equivalents of benzylamine indiethyl ether at room temperature to produce pyrroles  7a , b in high yields. The corresponding  N  -methyl compound  7c was obtained in moderate yield upon bubbling of gaseousmethylamine through an ethereal solution of 7-bromo-heptan-2,5-dione  4b .2-(2-Succinimido)pyrroles  7d – f   were prepared in a similarway to that of compounds  7a – c  (Scheme 2). However, theuse of   b -bromoketones  4a , b  as precursors of pyrroles  7d – f  resulted only in moderate yields of the target products.Better results were achieved by preliminary transformationof the protected bromoketones  5a , b  into the correspondingvinyl ketones  8a , b  followed by reaction of the latter enoneswith equimolar quantities of succinimide and catalyticamounts of K  2 CO 3  and triethylamine. The use of either of these catalysts separately, led to an extension of the reactiontime which may be due to the non-sufficient solubility of potassium carbonate and deficient basicity of triethylamine.Combined use of these bases probably evoked phasetransfer catalytic processes. To remove the acetal protectinggroup, the resulting crude product was treated with acetonein the presence of   p -toluenesulfonic acid or cation exchangeresin (in H þ -form). The use of the latter in the synthesis of  9a  allows simplification of the work-up procedure and anincrease in the yield of the product. To obtain the pyrroles 7d – f  , the corresponding dicarbonyl compounds  9a , b  wereinvolved in a heterocyclization reaction with benzylamineor methylamine.  N  ,  N  0 -Dialkyl-2-(2-aminoethyl)pyrroles  7a – c  were con-verted into the target fused compounds  10a – i  by Pictet–Spengler condensation with aromatic aldehydes in  i -PrOH(Scheme 3). The reaction was complete within 2–4 h atroom temperature, and tetrahydropyrrolopyridines  10a – g precipitated from the reaction mixture as crystallineproducts (80–90% yield after recrystallisation from i -PrOH). Pyrrolopyridines  10h , i  having no substituents atthe  a -position of the pyrrole ring, were obtained in similarmanner at 0 8 C, and were isolated by column chromato-graphy with somewhat lower yields. It should be noted thatin contrast to the reported procedure, 5 a non-catalyticvariant of the Pictet–Spengler reaction was used whichallowed us to isolate acidophobic compounds  10h , i  as freebases in good yields. Scheme 3.Scheme 4.  M. V. Raiman et al. / Tetrahedron 59 (2003) 5265–5272  5267  2-(2-Succinimidoethyl)pyrroles  7d – f   were converted intothe corresponding pyrroloindolizines  13a – c  by a modifiedPictet–Spengler reaction in which the heterocyclizationsteps were achieved by the intramolecular electrophilicaddition of   N  -acyliminium ion generated from the partiallyreduced succinimide fragment of compounds  11a – c (Scheme 4). The latter were obtained in quantitative yieldsby treatment of pyrroles  7d – f   with sodium borohydride in aCH 3 OH-THF mixture at 2 10 8 C. 12 The formation of the hemiaminals  11a – c  was supportedspectroscopically by the appearance of the characteristicmultiplet of the methine proton at 4.86–4.98 ppm in the  1 HNMR spectra (CDCl 3 ). The hemiaminals  11b , c , withoutpurification, were cyclized upon reaction with mesylchloride in dichloromethane in the presence of triethylamineto give tricyclic pyrrolopyridine derivatives  12b , c  in goodyields, whereas the less substituted pyrrole  11a  turned into aresin-like product under these conditions. The conversion of hemiaminal  11a  into pyrroloindolizidine  12a  was success-fully achieved by treatment with oxalic acid on silica indiethyl ether. The structure of compounds  12a – c  wasconfirmed by the  1 H NMR spectra (CDCl 3 ), which revealeda characteristic triplet of doublets at 2.86–3.06 (  J  gem <  J  aa ¼ 12.0 Hz;  J  ae ¼ 5.5 Hz) for the axial 5-H proton and adoublet of doublets at 4.32–4.48 (  J  gem ¼ 12.0 Hz;  J  ea ¼ 5.5 Hz;  J  ee ¼ 0 Hz) for the equatorial 5-H protondeshielded due to the anisotropic effect of the amidecarbonyl. 13 The amide moiety of compounds  12a – c  was reduced using1 M borane in tetrahyrofuran, 14 and the resulting com-pounds  13a – c  were purified by column chromatography.The NMR spectra (CDCl 3 ) of the products  13a – c  showedan upfield shift of the equatorial 5-H proton signal (4.32–4.48 ppm in the spectra of   12a – c ).In conclusion, an effective route to substituted 4,5,6,7-tetrahydro-1  H  -pyrrolo[3,2- c ]pyridines and related4,5,7,8,9,9a-hexahydro-3  H  -pyrrolo[2,3- g ]indolizines wasdeveloped, starting from acetals of ethyl 4-oxoalkanoatesvia the preparation of latent vinyl 1,4-dicarbonyl com-pounds as the key intermediates. 3. Experimental3.1. General IR spectra were measured on a Specord 75 IR spectro-photometer.  1 H NMR spectra were recorded at 60 MHz(Tesla BS-467) in CCl 4  with hexamethyldisiloxane asthe internal standard, or 200 MHz (Bruker-200) withTMS as the internal standard, or 400 MHz (Bruker Avance400) with CDCl 3  as the solvent.  13 C NMR spectra wererecorded with a Bruker Avance 400 at 100.6 MHz withCDCl 3  as solvent. Melting points were determined in opencapillaries and are uncorrected. Preparative columnchromatography was carried out on silica gel (Merck;70–230 Mesh). All chemicals were reagent grade; solventswere dried and distilled prior to use. The cation exchangerresin (in H þ -form) was obtained from the ReakhimCompany.The cyclopropanols  2b ,  3  were prepared according to theknown procedures. 8e 3.1.1. 1-(3,3-Diethoxypropyl)-1-cyclopropanol (2a).  Asolution of ethylmagnesium bromide in Et 2 O (5 mL of 3.2 M solution, 16 mmol) was added to a stirred solution of ethyl 4,4-diethoxybutanoate  1a  (1 g, 4.9 mmol) and Ti(OPr- i ) 4  (0.15 mL, 0.49 mmol) in dry Et 2 O (10 mL) at roomtemperature over 10 min. The reaction mixture was stirredfor 1 h and quenched with an ice-cold saturated aqueoussolution of NH 4 Cl (10 mL). After filtration, the organiclayer was separated and the aqueous phase was extractedwith Et 2 O (3 £ 3 mL). The organic phases were combined,washed with brine, dried with Na 2 SO 4  and evaporated invacuo. The crude product was purified by columnchromatography on silica gel (Et 2 O–cyclohexane, 1:3) togive 0.78 g (85%) of cyclopropanol  2a  as a colorless oil.  1 HNMR (400 MHz, CDCl 3 ):  d   0.38–0.41 (m, 2H), 0.69–0.72(m, 2H), 1.18 (t,  J  ¼ 7.2 Hz, 6H), 1.62 (t,  J  ¼ 7.2 Hz, 2H),1.85 (dt,  J  ¼ 7.2, 5.1 Hz, 2H), 3.48 (dq,  J  ¼ 9.2, 7.2 Hz, 2H),3.64 (dq,  J  ¼ 9.2, 7.2 Hz, 2H), 3.80 (bs, 1H), 4.56 (t,  J  ¼ 5.1 Hz, 1H).  13 C NMR (CDCl 3 ):  d   13.5, 15.1, 30.5, 33.4,55.0, 61.1, 102.9. Anal. calcd for C 10 H 20 O 3 : C, 63.83; H,10.64. Found: C, 63.88; H, 10.63. 3.1.2. 1-Benzyl-2-[2-(benzylamino)ethyl]pyrrole (7a). Bromine-pyridine complex (0.99 g, 4.15 mmol) was addedportionwise to a stirred solution of cyclopropanol  2a (0.78 g, 4.15 mmol) in dry Et 2 O (10 mL) at 10 8 C over10 min. The precipitate was removed by filtration and thesolvent evaporated in vacuo to give the crude  b -bromo-ketone  5a . The latter was dissolved in 15 mL of acetone and0.4 g of cation exchange resin in H þ -form was added. Afterstirring for 2 h the cation exchange resin was removed byfiltration and the solvent was evaporated. The residue wasdissolved in 15 mL of ether and the resulting solution of  b -bromoketone  4a  was added dropwise to a vigorouslystirred solution of benzylamine (1.36 mL, 12.45 mmol) in15 mL of diethyl ether over 30 min. The precipitate wasfiltered, the solution washed with water, brine, filteredthrough a thick layer of alumina and dried over Na 2 SO 4 .Evaporation of the solvent followed by purification of thecrude product on a column of silica (Et 2 O–petroleum ether,1:1) gave 0.92 g (76%) of   b -(aminoethyl)pyrrole  7a  as ayellowish oil. IR (CHCl 3 ):  n  max  3346 cm 2 1 .  1 H NMR(400 MHz, CDCl 3 ):  d   1.54 (bs, 1H), 2.69 (t,  J  ¼ 7.2 Hz, 2H),2.80 (t,  J  ¼ 7.2 Hz, 2H), 3.71 (s, 2H), 5.03 (s, 2H), 5.88–6.00(m, 1H), 6.12–6.14 (m, 1H), 6.62–6.64 (m, 1H), 6.94–6.97(m, 2H), 7.20–7.33 (m, 8H).  13 C NMR (CDCl 3 ):  d   26.8,48.25, 50.3, 53.8, 107.1, 107.7, 121.3, 126.2, 126.85, 127.3,128.0, 128.3, 128.7, 138.4. Anal. calcd for C 20 H 22 N 2 : C,82.76; H, 7.59. Found: C, 83.15H, 7.56. 3.1.3. 1-Benzyl-2-[2-(benzylamino)ethyl]-5-methylpyr-role (7b).  NBS (1.78 g, 10 mmol) was added in threeportions to an ice-cold solution of cyclopropanol  3 8e (1.28 g,10 mmol) in CCl 4  (25 mL). After stirring for 1 h theprecipitate was filtered off, and the filtrate was evaporated invacuo to give 2 g of the crude  b -bromoketone  4b  as ayellowish liquid (100%). Owing to the lability of thiscompound, it was used further without purification.Benzylamine (3.33 mL, 30 mmol) was added to a solutionof   b -bromoketone  4b  in Et 2 O (25 mL). The reaction  M. V. Raiman et al. / Tetrahedron 59 (2003) 5265–5272 5268  mixture was stirred at room temperature for 2 h andevaporated in vacuo. Column chromatography of theresidue on alumina (EtOAc–cyclohexane, 1:1) led to2.74 g (90%) of aminoethylpyrrole  7b  as a yellowish oil.IR (CHCl 3 ):  n  max  3327 cm 2 1 .  1 H NMR (200 MHz, CDCl 3 ): d   1.77 (bs, 1H), 2.14 (s, 3H), 2.62–2.84 (m, 4H), 3.68 (s,2H), 5.02 (s, 2H), 5.84–5.88 (m, 2H), 6.76–6.92 (m, 2H),7.14–7.36 (m, 8H).  13 C NMR (CDCl 3 ):  d   12.2, 26.7, 46.4,48.2, 53.6, 105.2, 105.6, 125.3, 126.7, 126.8, 127.9, 128.1,128.2, 128.5, 129.8, 138.4, 140.1. Anal. calcd for C 21 H 24 N 2 :C, 82.84; H, 7.96. Found: C, 82.70; H, 7.78. 3.1.4. 1,5-Dimethyl-2-[2-(methylamino)ethyl]pyrrole(7c).  Through a solution of the crude  b -bromoketone  4b (2.1 g, 10 mmol), in benzene (25 mL) methylamine(5–7 equiv.) was bubbled during 15 min. The reactionmixture was stirred at room temperature for 8 h andevaporated in vacuo. The aminoethylpyrrole  7c  was isolatedas a yellowish oil by column chromatography on alumina(EtOAc–cyclohexane, 1:1). Yield: 0.99 g (65%). IR(CHCl 3 ):  n  max  3360 cm 2 1 .  1 H NMR (400 MHz, CCl 4 ):  d  2.11 (bs, 1H); 2.25 (s, 3H); 2.50 (s, 3H); 2.72–2.90 (m, 4H);3.45 (s, 3H); 5.78–5.92 (m, 2H).  13 C NMR (CDCl 3 ):  d   12.3,26.9, 29.9, 36.1, 50.7, 104.4, 104.8, 128.1, 128.6. Anal.calcd for C 9 H 16 N 2 : C, 70.99; H, 10.61. Found: C, 71.07; H,10.44. 3.1.5. 6,6-Diethoxy-1-hexen-3-one (8a).  Bromine-pyridinecomplex (1.5 g, 6.3 mmol) was added portionwise over20 min to a stirred solution of cyclopropanol  2a  (1.18 g,6.3 mmol) in dry Et 2 O (20 mL) at 10 8 C. The precipitate wasremoved by filtration, and triethylamine (0.92 mL,6.6 mmol) was added dropwise to the filtrate. After stirringfor 3 h at room temperature followed by filtration of theprecipitate, the reaction mixture was evaporated in vacuo.The crude product was purified by column chromatographyon silica gel (Et 2 O–petroleum ether, 35:65) to give 0.97 g(83%) of compound  8a  as a colorless oil. IR (CHCl 3 ):  n  max 1673, 1612 cm 2 1 .  1 H NMR (400 MHz, CDCl 3 ):  d   1.16 (t,  J  ¼ 7.2 Hz, 6H), 1.91 (dt,  J  ¼ 7.2, 5.1 Hz, 2H), 2.65 (t,  J  ¼ 7.2 Hz, 2H), 3.45 (dq,  J  ¼ 9.2, 7.2 Hz, 2H), 3.61 (dq,  J  ¼ 9.2, 7.2 Hz, 2H), 4.48 (t,  J  ¼ 5.1 Hz, 1H), 5.79 (dd,  J  ¼ 10.8, 1.5 Hz, 1H), 6.20 (dd,  J  ¼ 17.4, 1.5 Hz, 1H), 6.32(dd,  J  ¼ 17.4, 10.8 Hz, 1H).  13 C NMR (CDCl 3 ):  d   15.2, 27.8,34.4, 61.6, 102.0, 127.7, 136.5, 200.0. Anal. calcd forC 10 H 18 O 3 : C, 64.52; H, 9.68. Found: C, 64.75; H, 9.66. 3.1.6. 5-(2-Methyl-1,3-dioxolan-2-yl)-1-penten-3-one(8b).  NBS (1.78 g, 10 mmol) was added in three portionsto an ice-cold solution of cyclopropanol  2b 8e (1.72 g,10 mmol) in CCl 4  (25 mL). After stirring for 1 h followedby filtration of precipitate, the reaction mixture wasevaporated in vacuo. The crude  b -bromoketone  5b  wasdissolved in Et 2 O (25 mL) and triethylamine (4.25 mL,30 mmol) was added. The reaction mixture was refluxed for1 h, the precipitate was filtered off, the solution was washedwith brine (15 mL), dried (Na 2 SO 4 ) and evaporated. Theproduct was purified by distillation in vacuo to give 1.36 g(80%) of ketone  8b  as a colorless liquid. Bp 78–80 8 C/ 2 Torr. IR (CHCl 3 ):  n  max  1680, 1627 cm 2 1 .  1 H NMR(60 MHz, CDCl 3 ):  d   1.25 (s, 3H), 2.0 (t,  J  ¼ 7.0 Hz, 2H),2.60 (t,  J  ¼ 7.0 Hz, 2H), 3.87 (s, 4H), 5.64–6.40 (m, 3H).  13 CNMR (CDCl 3 ):  d   23.7, 32.6, 33.9, 64.4, 109.0, 127.5, 136.2,199.9. Anal. calcd for C 9 H 14 O 3 : C, 63.50; H, 8.31. Found:C, 63.59; H, 8.26. 3.1.7. 4-Oxo-6-succinimidohexanal (9a).  K  2 CO 3  (0.07 g,0.5 mmol) and triethylamine (0.07 mL, 0.5 mmol) wereadded to a solution of 6,6-diethoxy-1-hexen-3-one  8a (0.94 g, 5 mmol) and succinimide (0.5 g, 5 mmol) in i -PrOH (10 mL). The reaction mixture was refluxed for1 h, cooled to room temperature and evaporated in vacuo.The residue was dissolved in Et 2 O (15 mL), washed withwater (2 £ 3 mL) and brine (3 mL), and dried over Na 2 SO 4 .The solvent was removed in vacuo, the residue wasdissolved in acetone (10 mL) and cation exchange resin inH þ -form (0.3 g) was added to the solution. After stirring for2 h the cation exchange resin was removed by filtration andthe solvent was evaporated. The residue was purified byrecrystallisation from  i -PrOH to give 0.85 g (80%) of aldehyde  9a  as white needles. Mp 85 8 C. IR (CHCl 3 ):  n  max 1689 cm 2 1 .  1 H NMR (400 MHz, CDCl 3 ):  d   2.72 (bs, 4H),2.74- 2.79 (m, 4H), 2.84 (t,  J  ¼ 7.2 Hz, 2H), 3.81 (t,  J  ¼ 7.2 Hz, 2H), 9.76 (s, 1H).  13 C NMR (CDCl 3 ):  d   28.1,33.8, 34.6, 37.4, 39.6, 176.9, 200.0, 205.7. Anal. calcd forC 10 H 13 NO 4 : C, 56.87; H, 6.16. Found: C, 57.11; H, 6.14. 3.1.8. 7-Succinimido-2,5-heptanedione (9b).  K  2 CO 3 (0.1 g, 0.7 mmol) and triethylamine (0.1 mL, 0.72 mmol)were added to a solution of ketone  8b  (1.7 g, 10 mmol) andsuccinimide (0.99 g, 10 mmol) in  i -PrOH (20 mL). Thereaction mixture was refluxed for 1 h. The volatilecompounds were removed in vacuo, water (20 mL) wasadded to the residue, and the mixture was extracted withdichloromethane (3 £ 15 mL). The organic phase waswashed with brine (15 mL), dried over Na 2 SO 4  andevaporated. To the residue was added acetone (10 mL),CH 2 Cl 2  (20 mL) and  p -toluenesulfonic acid (0.02 g,0.1 mmol), and the mixture was refluxed for 1.5 h. Afterevaporation of the solvent in vacuo the residue wasdissolved in CH 2 Cl 2  (20 mL), washed with brine(3 £ 10 mL) and dried over Na 2 SO 4 . The solvent wasremoved and the product was recrystallised from  i -PrOHto give 2.08 g (92%) of compound  9b  as white needles. Mp65–68 8 C. IR (CHCl 3 ):  n  max  1707 cm 2 1 .  1 H NMR(200 MHz, CDCl 3 ):  d   2.20 (s, 3H), 2.62–2.78 (m, 8H),2.82 (t,  J  ¼ 7.0 Hz, 2H), 3.78 (t,  J  ¼ 7.0 Hz, 2H).  13 C NMR(CDCl 3 ):  d   28.1, 29.8, 33.8, 36.0, 36.8, 39.6, 176.9, 206.4,206.8. Anal. calcd for C 11 H 15 NO 4 : C, 58.65; H, 6.73.Found: C, 58.44; H, 6.60. 3.1.9. 1-Benzyl-2-(2-succinimidoethyl)pyrrole (7d). Benzylamine (0.1 mL, 0.9 mmol) was added to a stirredsolution of ketoaldehyde  9a  (0.19 g, 0.9 mmol) in methanol(5 mL) at 30 8 C. The reaction mixture was stirred for 10 minand the solvent was evaporated in vacuo. Columnchromatography of the residue on silica gel (Et 2 O–petroleum ether; 35:65) gave 0.23 g (91%) of compound 7d  as white crystals. Mp 107 8 C. IR (CHCl 3 ):  n  max 1680 cm 2 1 .  1 H NMR (400 MHz, CDCl 3 ):  d   2.64 (bs, 4H),2.76 (t,  J  ¼ 7.7 Hz, 2H), 3.67 (t,  J  ¼ 7.7 Hz, 2H), 5.12 (s, 2H),6.01 (m, 1H), 6.11 (dd,  J  ¼ 3.5, 2.8 Hz, 1H), 6.64 (dd,  J  ¼ 2.8,1.8 Hz, 1H), 7.01–7.03 (m, 2H), 7.23–7.32 (m, 3H).  13 CNMR (CDCl 3 ):  d   24.2, 28.0, 38.0, 50.2, 107.2, 107.7, 121.8,126.3, 127.3, 128.3, 128.6, 138.2, 176.8. Anal. calcd forC 17 H 18 N 2 O 2 : C, 72.34; H, 6.38. Found: C, 72.58; H, 6.32.  M. V. Raiman et al. / Tetrahedron 59 (2003) 5265–5272  5269
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