Water → 1-(4-Chloro-2-fluorophenyl)-1-cyclopropylethanol

HRID 561417Notes

Reaction equation

[CH:1]1([Mg]Br)[CH2:3][CH2:2]1.[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([C:13](=[O:15])[CH3:14])=[C:9]([F:16])[CH:8]=1.C(#N)C.O>O1CCCC1.C(OCC)C>[Cl:6][C:7]1[CH:12]=[CH:11][C:10]([C:13]([CH:1]2[CH2:3][CH2:2]2)([OH:15])[CH3:14])=[C:9]([F:16])[CH:8]=1

Participants

Conditions

Temperature: 0 °C

Procedure

114.6 ml (57.31 mmol) of a 0.5N solution of cyclopropylmagnesium bromide in tetrahydrofuran were taken up at 0° C. in 23 ml of diethyl ether, and 4.95 g (28.65 mmol) of 4′-chloro-2′-fluoroacetophenone dissolved in 5 ml of diethyl ether were slowly added dropwise. Stirring at 0° C. for 1 h was followed by warming to RT, and the reaction solution was mixed with acetonitrile, water and a little kieselguhr, and the mixture was filtered through kieselguhr. The phases of the filtrate were separated and the aqueous phase was extracted twice with diethyl ether. The combined organic phases were washed with saturated aqueous sodium chloride solution and dried over sodium sulfate, and the solvents were removed in vacuo. The crude product was purified by preparative HPLC (mobile phase: acetonitrile-water gradient) to result in 4.30 g (70% of theory) of the title compound.

Workup

additionwere slowly added dropwise
temperatureby warming to RT
filtrationa little kieselguhr, and the mixture was filtered through kieselguhr
customThe phases of the filtrate were separated
extractionthe aqueous phase was extracted twice with diethyl ether
washThe combined organic phases were washed with saturated aqueous sodium chloride solution
dry with materialdried over sodium sulfate
customthe solvents were removed in vacuo
customThe crude product was purified by preparative HPLC (mobile phase: acetonitrile-water gradient)

Sources & evidence

ORD record: ord-1d5a59cdad564880834e092844786c49
Source dataset: uspto-grants-2011_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08063234B2

Reaction notes

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