1,6-Dibromohexane → 1-(2-[(6-Bromohexyl)oxy]-1,1-difluoroethyl)-3-methoxybenzene
Reaction equation
[F:1][C:2]([F:13])([C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH3:12])[CH:6]=1)[CH2:3][OH:4].[H-].[Na+].[Br:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]Br>CN(C)C=O.C(Cl)Cl>[Br:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][O:4][CH2:3][C:2]([C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([O:11][CH3:12])[CH:6]=1)([F:13])[F:1]Participants
6
Procedure
To a cooled solution of Intermediate 68 (3.19 g, 16.95 mmol) in dimethylformamide (20 mL) was added 60% sodium hydride (1.36 g, 33.9 mmol) and 1,6-dibromohexane (5.2 mL, 33.9 mmol). The mixture was stirred at room temperature for 2 hours. The crude was diluted with methylene chloride (50 mL) and washed with water (3×50 mL), dried (MgSO4) and concentrated. The excess of 1,6-dibromohexane was eliminated by distillation at reduced pressure (P=0.15-0.18 mmHg, T=60-65° C.) and the crude was purified by column chromatography with silica gel using methylene chloride as eluent. The title compound was obtained (3.41 g, 57%) as oil.
Workup
- washwashed with water (3×50 mL)
- dry with materialdried (MgSO4)
- concentrationconcentrated
- distillationThe excess of 1,6-dibromohexane was eliminated by distillation at reduced pressure (P=0.15-0.18 mmHg, T=60-65° C.)
- customthe crude was purified by column chromatography with silica gel
Sources & evidence
- ORD record
- ord-8c13e1e785b34f288b920321ae1d7b90
- Source dataset
- uspto-grants-2012_08
- Patent number
- US08242177B2
Reaction notes
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