1,4-Dibromobenzene → (2S)-2-{(S)-[(4-bromophenyl)-(2,4-difluorophenyl)-methyl]-amino}-4-methylpentan-1-ol

HRID 1880538Notes

Reaction equation

HRID 1880538 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([Br:8])=[CH:4][CH:3]=1.[Li]CCCC.[F:14][C:15]1[CH:29]=[C:28]([F:30])[CH:27]=[CH:26][C:16]=1[CH:17]=[N:18][CH:19]([CH2:22][CH:23]([CH3:25])[CH3:24])[CH2:20][OH:21]>CCOCC>[Br:8][C:5]1[CH:6]=[CH:7][C:2]([C@H:17]([NH:18][C@@H:19]([CH2:22][CH:23]([CH3:25])[CH3:24])[CH2:20][OH:21])[C:16]2[CH:26]=[CH:27][C:28]([F:30])=[CH:29][C:15]=2[F:14])=[CH:3][CH:4]=1

Participants

5

Reactant 3

HCID 78041,4-DibromobenzeneHCID 574469542-[(2,4-Difluorobenzylidene)-amino]-4-methylpentan-1-olHCID 178418339Butyllithium

Product 1

HCID 67298634(2S)-2-{(S)-[(4-bromophenyl)-(2,4-difluorophenyl)-methyl]-amino}-4-methylpentan-1-ol

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

To a solution of 1,4-dibromobenzene (24.5 g, 100 mmol, 5 eq) in dry ether (200 mL) under nitrogen atmosphere at −30° C., nBuLi (64.75 mL, 1.6 M solution in hexanes, 5 eq) was added and the reaction mixture was stirred for 1 h. A solution of 2-[(2,4-difluorobenzylidene)-amino]-4-methylpentan-1-ol (5 g, 20 mmol) in dry ether was added slowly at −30° C. After stirring for 4 h, the reaction was quenched with water. The ether layer was washed with saturated solution of NaCl, and dried over MgSO4. The solvent was removed under reduced pressure and the crude was flash chromatographed on 500 cm3 of silica gel using 8:2 hexanes:EtOAc as an eluant to yield (2S)-2-{(S)-[(4-bromophenyl)-(2,4-difluorophenyl)-methyl]-amino}-4-methylpentan-1-ol.

Workup

  1. stirringAfter stirring for 4 h
  2. customthe reaction was quenched with water
  3. washThe ether layer was washed with saturated solution of NaCl
  4. dry with materialdried over MgSO4
  5. customThe solvent was removed under reduced pressure
  6. customchromatographed on 500 cm3 of silica gel using 8:2 hexanes

Sources & evidence

ORD record
ord-d65471211da64ec2986d443ead537f2c
Source dataset
uspto-grants-2012_11
Patent number
US08318748B2

Reaction notes

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