Diethyl Ether → 2-(2-Chloro-5-fluoropyrimidin-4-yl)propan-2-ol

HRID 338065Notes

Reaction equation

[Cl:1][C:2]1[N:7]=[C:6]([C:8](=[O:10])[CH3:9])[C:5]([F:11])=[CH:4][N:3]=1.[CH3:12][Mg]Br.C(OCC)C>O1CCCC1>[Cl:1][C:2]1[N:7]=[C:6]([C:8]([OH:10])([CH3:12])[CH3:9])[C:5]([F:11])=[CH:4][N:3]=1

Participants

Conditions

Temperature: -78 °C

Procedure

A stirred, −78° C. solution of 1-(2-chloro-5-fluoro-pyrimidin-4-yl)ethanone (10.06 g, 57.6 mmol) in tetrahydrofuran (100 mL) under nitrogen is reacted with a 3 M solution of methyl magnesium bromide in diethyl ether (124 mL, 72.04 mmol) and the resulting mixture is stirred at −78° C. for 20 minutes. The reaction is quenched with aqueous saturated ammonium chloride and the mixture is warmed to room temperature. The reaction mixture is extracted three times with ethyl acetate. The combined organic layers are dried over sodium sulfate and concentrated under vacuum. The crude product is purified over silica gel with a 30 minute, 5% to 100% ethyl acetate in hexanes gradient, to give the title compound (7.06 g, 64%). ES/MS (m/e): (35Cl/37Cl) 191/193 (M+H).

Workup

customThe reaction is quenched with aqueous saturated ammonium chloride
temperaturethe mixture is warmed to room temperature
extractionThe reaction mixture is extracted three times with ethyl acetate
dry with materialThe combined organic layers are dried over sodium sulfate
concentrationconcentrated under vacuum
customThe crude product is purified over silica gel with a 30 minute

Sources & evidence

ORD record: ord-5609727a6b934b1b957d7da1f1fae8c2
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08889856B2

Reaction notes

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