Tetrahydrofuran → (2S,3S,alphaS)-t-Butyl 3-(N-allyl-alpha-methylbenzylamino)-2-hydroxy-3-phenylpropionate

HRID 1637039노트

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HRID 1637039 반응식
[CH2:1]([NH:4][C@@H:5]([CH3:12])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[CH:2]=[CH2:3].C([Li])CCC.[NH2-].[Li+].[C:20]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])(=[O:29])[CH:21]=[CH:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1.[O:35]1CCCC1>>[CH2:1]([N:4]([C@@H:5]([CH3:12])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)[C@@H:22]([C:23]1[CH:24]=[CH:25][CH:26]=[CH:27][CH:28]=1)[C@H:21]([OH:35])[C:20]([O:30][C:31]([CH3:34])([CH3:33])[CH3:32])=[O:29])[CH:2]=[CH2:3]

참가 물질

6

반응물 5

HCID 8028Tetrahydrofuran3회HCID 24532Lithium amideHCID 347555Tert-butyl cinnamateHCID 10899069(S)-N-allyl-alpha-methylbenzylamineHCID 178418339Butyllithium

생성물 1

HCID 86755227(2S,3S,alphaS)-t-Butyl 3-(N-allyl-alpha-methylbenzylamino)-2-hydroxy-3-phenylpropionate수율 95%

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온도
0 °C

실험 절차

A solution of (S)-N-allyl-α-methylbenzylamine (2) (1.94 g, 12.1 mmol) in anhydrous tetrahydrofuran (25 ml) was cooled to -78° C. and 1.6M butyllithium (6.03 ml, 9.6 mmol) was added dropwise via a syringe. The resulting orange lithium amide solution was stirred at -78° C. for 1 hour. A solution of t-butyl cinnamate (7) (1.64 g, 8.1 mmol) in anhydrous tetrahydrofuran (15 ml) was then added via a cannula and the solution was stirred for a further 1 hour. The resulting yellow enolate solution was then diluted with anhydrous tetrahydrofuran (30 ml) and solid (+)-(camphorsulphonyl)-oxaziridine (2.76 g, 12.1 mmol) was added. After stirring for a further 6 hours at -78° C., the mixture was warmed to 0° C. (15 minutes) and quenched by the addition of saturated aqueous ammonium chloride solution. Ethyl acetate (50 ml) was added, followed by brine (10 ml). The organic layer was separated, dried (magnesium sulphate) and filtered and the solvent was evaporated under reduced pressure to afford an oily solid residue. Treatment of this with diethyl ether precipitated the oxaziridine/sulfonimine which was removed by filtration and the resulting oil was purified by flash chromatography on silica gel [ethyl acetate/petroleum ether (1:19)] affording the title compound (Rf 0.20) as a colourless oil (2.89 g, 95%). δH (300 MHz: CDCl3) 7.50-7.21 (10H, m, Ph), 5.89 (1H, m, NCH2CH=CH2), 5.12 (1H, app. dd, J=17.2 and 41.4, trans CH=CH2), 5.04 (1H, app. dd, J=17.2 and 1.4, cis CH=CH2), 4.53 (1H, d, J=3.8, CHOH), 4.23 (1H, d, J=3.8, NCHCH), 4.13 (1H, q, J=6.8, PhCHCH3), 3.47 (1H, app. dd, J=15.6 and 7.1, NCH2), 3.03 (1H, bs, OH), 1.29 (9H, s, (CH3)3CH), 1.21 (3H, d, J=6.8, PhCHCH3).

후처리

  1. additionwas added
  2. stirringAfter stirring for a further 6 hours at -78° C.
  3. customquenched by the addition of saturated aqueous ammonium chloride solution
  4. additionEthyl acetate (50 ml) was added
  5. customThe organic layer was separated
  6. dry with materialdried (magnesium sulphate)
  7. filtrationfiltered
  8. customthe solvent was evaporated under reduced pressure
  9. customto afford an oily solid residue
  10. customTreatment of this with diethyl ether precipitated the oxaziridine/sulfonimine which
  11. customwas removed by filtration
  12. customthe resulting oil was purified by flash chromatography on silica gel [ethyl acetate/petroleum ether (1:19)]

출처 및 근거

ORD 기록
ord-d3e3070c22f94780ac41c28852b17675
출처 데이터셋
uspto-grants-2000_03
특허 번호
US06037498

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