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

HRID 1436480ノート

反応式

HRID 1436480 の反応式
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]

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

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%).

後処理

  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

出典と根拠

ORDレコード
ord-23097f95fc894513bc44cbb7fbbe93dd
出典データセット
uspto-grants-2009_11
特許番号
US07618978B2

反応ノート

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