2-Bromopyridine → 2-(S)-[Bis-(2-methylbenzyl)-amino]-3-(3,5-difluorophenyl)-1-pyridin-2-yl-propan-1-(S)-ol

HRID 1436480노트

반응식

HRID 1436480 반응식
Br[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1.C([Li])CCC.[CH3:13][C:14]1[CH:41]=[CH:40][CH:39]=[CH:38][C:15]=1[CH2:16][N:17]([CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[CH3:37])[C@@H:18]([CH2:21][C:22]1[CH:27]=[C:26]([F:28])[CH:25]=[C:24]([F:29])[CH:23]=1)[CH:19]=[O:20]>C1COCC1>[CH3:13][C:14]1[CH:41]=[CH:40][CH:39]=[CH:38][C:15]=1[CH2:16][N:17]([CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=1[CH3:37])[C@@H:18]([CH2:21][C:22]1[CH:23]=[C:24]([F:29])[CH:25]=[C:26]([F:28])[CH:27]=1)[C@@H:19]([C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][N:3]=1)[OH:20]

참가 물질

5

반응물 3

HCID 79732-BromopyridineHCID 866149922-(S)-[bis-(2-methylbenzyl)-amino]-3-(3,5-difluorophenyl)-propionaldehydeHCID 178418339Butyllithium

생성물 1

HCID 690178192-(S)-[Bis-(2-methylbenzyl)-amino]-3-(3,5-difluorophenyl)-1-pyridin-2-yl-propan-1-(S)-ol수율 40.8%

시약·촉매·용매 1

HCID 8028Tetrahydrofuran용매2회

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온도
-78 °C

실험 절차

Dissolve 2-bromopyridine (0.485 mL, 5.07 mmol) in THF (30 mL) and cool to −78° C. Add n-butyllithium (2.0 mL, 2.5 M in hexanes). Slowly add 2-(S)-[bis-(2-methylbenzyl)-amino]-3-(3,5-difluorophenyl)-propionaldehyde (1.37 g, 3.3 mmol) in THF (10 mL) and stir 2 h. Quench reaction with saturated aqueous ammonium chloride. Warm to room temperature. Wash organic layer twice with 5% aqueous citric acid, saturated aqueous sodium chloride, dry (magnesium sulfate), concentrate and purify twice (silica gel chromatography, eluting with hexanes and ethyl acetate, and then dichloromethane and ethyl acetate) to give the title compound as a foam (0.636 g, 40%).

후처리

  1. customQuench
  2. customreaction with saturated aqueous ammonium chloride
  3. temperatureWarm to room temperature
  4. dry with materialWash organic layer twice with 5% aqueous citric acid, saturated aqueous sodium chloride, dry (magnesium sulfate)
  5. concentrationconcentrate
  6. custompurify twice (silica gel chromatography
  7. washeluting with hexanes and ethyl acetate

출처 및 근거

ORD 기록
ord-23097f95fc894513bc44cbb7fbbe93dd
출처 데이터셋
uspto-grants-2009_11
특허 번호
US07618978B2

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