(Diethylamino)sulfur trifluoride → 2-Chloro-5-fluoro-4-(1-fluoro-1-methyl-ethyl)pyrimidine

HRID 338066Notes

Reaction equation

C(N(S(F)(F)[F:7])CC)C.[Cl:10][C:11]1[N:16]=[C:15]([C:17](O)([CH3:19])[CH3:18])[C:14]([F:21])=[CH:13][N:12]=1>ClCCl>[Cl:10][C:11]1[N:16]=[C:15]([C:17]([F:7])([CH3:19])[CH3:18])[C:14]([F:21])=[CH:13][N:12]=1

Participants

Conditions

Temperature: -78 °C

Procedure

Diethylaminosulfur trifluoride (6.53 g, 40.5 mmol) is added drop wise to a −78° C. solution of 2-(2-chloro-5-fluoro-pyrimidin-4-yl)propan-2-ol (4.825 g, 25.31 mmol) in dichloromethane (70 mL) under nitrogen. The reaction is stirred at −78° C. for 30 minutes under nitrogen, is then quenched with aqueous saturated sodium bicarbonate and 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 resulting crude product is purified over silica gel with a 40 minute, 5% to 100% ethyl acetate in hexanes gradient to give the title compound (4.23 g, 87%). ES/MS (m/e): (35Cl/37Cl) 193/195 (M+H).

Workup

customis then quenched with aqueous saturated sodium bicarbonate
temperatureis 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 resulting crude product is purified over silica gel with a 40 minute

Sources & evidence

ORD record: ord-16546ef09df94f6382773454c75146a6
Source dataset: uspto-grants-2014_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08889856B2

Reaction notes

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