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

HRID 607508Notes

Reaction equation

C1COCC1.[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]>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 THF (100 ml) solution of 1,3-difluoro-5-methoxybenzene (7 g, 48.6 mmol) was added dropwise 1.6 M hexane solution of n-butyllithium (30 ml, 48.6 mmol) at −78° C. over 30 minutes and the mixture was stirred for 2 hours at −78° C. Then 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. After stirring at room temperature for an additional 1 hour, the reaction was quenched with water. The whole was extracted with EtOAc and the organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. Purification by silica gel column chromatography eluting with hexane/EtOAc (10:1) gave the title compound (9.7 g, 78% yield) as a colorless oil.

Workup

stirringthe mixture was stirred for 2 hours at −78° C
stirringAfter stirring at room temperature for an additional 1 hour
customthe reaction was quenched with water
extractionThe whole was extracted with EtOAc
dry with materialthe organic layer was dried over sodium sulfate
filtrationfiltered
concentrationconcentrated in vacuo
customPurification by silica gel column chromatography
washeluting with hexane/EtOAc (10:1)

Sources & evidence

ORD record: ord-fc4d75dbe60b445da0f07d6e59b6cc39
Source dataset: uspto-grants-2011_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07915448B2

Reaction notes

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