Water → 1-Fluoro-3-((R)-2,2,2-trifluoro-1-methylethoxymethyl)benzene

HRID 83530Notes

Reaction equation

[H-].[Na+].Br[CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[CH:6]=1.O.[F:13][C:14]([F:19])([F:18])[C@H:15]([OH:17])[CH3:16]>CN(C)C=O>[F:11][C:7]1[CH:8]=[CH:9][CH:10]=[C:5]([CH2:4][O:17][C@H:15]([CH3:16])[C:14]([F:19])([F:18])[F:13])[CH:6]=1

Participants

Conditions

Temperature: 0 °C

Procedure

Under argon atmosphere, a suspension of sodium hydride (76 mg, 60 wt % oil dispersion) in N,N-dimethylformamide (2.0 ml) was cooled to 0° C., a solution of N,N-dimethylformamide (2.0 ml) in (R)-1,1,1-trifluoropropan-2-ol (219 mg) was added thereto, and the mixture was stirred for 25 minutes. Then, a solution of 1-bromomethyl-3-fluorobenzene (297 mg) in N,N-dimethylformamide (2.0 ml) was added thereto, and then the mixture was stirred for 2 hours. To this reaction mixture was added water, and the mixture was extracted with ethyl acetate. This organic layer was washed with a saturated aqueous solution of sodium chloride, dried over anhydrous magnesium sulfate, and then concentrated under reduced pressure. The resulting residue was purified by silica gel thin-layer chromatography (eluent: n-hexane/ethyl acetate=9/1) to give the titled compound (242 mg).

Workup

stirringthe mixture was stirred for 2 hours
extractionthe mixture was extracted with ethyl acetate
washThis organic layer was washed with a saturated aqueous solution of sodium chloride
dry with materialdried over anhydrous magnesium sulfate
concentrationconcentrated under reduced pressure
customThe resulting residue was purified by silica gel thin-layer chromatography (eluent: n-hexane/ethyl acetate=9/1)

Sources & evidence

ORD record: ord-0acbc048256648b3992e9eb1dbf63a17
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08846746B2

Reaction notes

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