Tetrahydrofuran → 2-(2,6-Difluoro-4-methoxyphenyl)-1,1,1-trifluoropropan-2-ol

HRID 230595Notes

Reaction equation

O1CCCC1.[F:6][C:7]1[CH:12]=[C:11]([O:13][CH3:14])[CH:10]=[C:9]([F:15])[CH:8]=1.C([Li])CCC.[F:21][C:22]([F:27])([F:26])[C:23]([CH3:25])=[O:24]>O.CCCCCC>[F:6][C:7]1[CH:12]=[C:11]([O:13][CH3:14])[CH:10]=[C:9]([F:15])[C:8]=1[C:23]([OH:24])([CH3:25])[C:22]([F:27])([F:26])[F:21]

Participants

Conditions

Temperature: -78 °C

Procedure

To a tetrahydrofuran (100 ml) solution of 1,3-difluoro-5-methoxybenzene (7 g, 48.6 mmol) was added 1.6 M hexane solution of n-butyllithium (30 ml, 48.6 mmol) dropwise at −78° C. over 30 minutes and the mixture was stirred for 2 hours at −78° C. 1,1,1-Trifluoroacetone (6.5 g, 58.3 mmol) was added at −78° C. and the mixture was stirred for 2 hours at −78° C. followed by additional stirring for 1 hour at room temperature. Then, the reaction was diluted with water and the product was extracted with ethyl acetate. Then, the organic layer was filtrated, evaporated and concentrated. The residue was purified by silica gel column chromatography, eluting with hexane/ethyl acetate (10:1), to furnish 9.7 g (78% yield) of the title compound as a colorless oil.

Workup

stirringthe mixture was stirred for 2 hours at −78° C.
stirringby additional stirring for 1 hour at room temperature
extractionthe product was extracted with ethyl acetate
filtrationThen, the organic layer was filtrated
customevaporated
concentrationconcentrated
customThe residue was purified by silica gel column chromatography
washeluting with hexane/ethyl acetate (10:1)

Sources & evidence

ORD record: ord-c74114da6e5640aa9a03302297da0c67
Source dataset: uspto-grants-2009_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07566739B2

Reaction notes

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