Water → (2S)-2-[(R)-[(4-bromophenyl)-(4-fluorophenyl)-methyl]-amino}-4-methylpentan-1-ol

HRID 1620942Notes

Reaction equation

Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][CH:3]=1.C([Li])CCC.[F:14][C:15]1[CH:29]=[CH:28][C:18]([CH:19]=[N:20][CH:21]([CH2:24][CH:25]([CH3:27])[CH3:26])[CH2:22][OH:23])=[CH:17][CH:16]=1.O>CCOCC>[Br:8][C:5]1[CH:6]=[CH:7][C:2]([C@H:19]([NH:20][C@@H:21]([CH2:24][CH:25]([CH3:27])[CH3:26])[CH2:22][OH:23])[C:18]2[CH:17]=[CH:16][C:15]([F:14])=[CH:29][CH:28]=2)=[CH:3][CH:4]=1

Participants

Conditions

Temperature: 0 °C

Procedure

To a solution of 1,4-dibromobenzene (11.4 g, 48.35 mmol) in ether (120 mL) at −30° C. was added n-butyllithium (24.2 mL, 2.0M cyclohexane solution) over 10 minutes. The reaction mixture was stirred for 45 minutes, whereupon a solution of (S) 2-[(4-fluorobenzylidene)-amino]-4-methylpentan-1-ol (maximum 2.16 g, 9.67 mmol from the previous step) in ether (30 mL) was added dropwise. After 2 hours, during which the reaction mixture was allowed to warm to 0° C., water (200 mL) was added. The product was extracted with ethyl acetate (150 mL), washed with brine (100 mL), dried over MgSO4, filtered, concentrated in vacuo, and purified on a short plug of silica gel (20% ethyl acetate/hexane elution) to give (2S)-2-{(R)-[(4-bromophenyl)-(4-fluorophenyl)-methyl]-amino}-4-methylpentan-1-ol.

Workup

additionwas added dropwise
extractionThe product was extracted with ethyl acetate (150 mL)
washwashed with brine (100 mL)
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated in vacuo
custompurified on a short plug of silica gel (20% ethyl acetate/hexane elution)

Sources & evidence

ORD record: ord-cd3a63ecf0a74fc7af0901ad1acbfe7c
Source dataset: uspto-grants-2014_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08772336B2

Reaction notes

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