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

HRID 1436480Notes

Reaction equation

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]

Participants

Conditions

Temperature: -78 °C

Procedure

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%).

Workup

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

Sources & evidence

ORD record: ord-23097f95fc894513bc44cbb7fbbe93dd
Source dataset: uspto-grants-2009_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07618978B2

Reaction notes

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