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

HRID 521701Notes

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, quenched with saturated aqueous sodium bicarbonate, and 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 using silica gel column chromatography using a 5-100% gradient of ethyl acetate in hexanes to give the title compound (4.23 g, 87%). ES/MS (m/e): 193 and 195 (M+1).

Workup

customquenched with saturated aqueous sodium bicarbonate
temperaturewarmed 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

Sources & evidence

ORD record: ord-bc0fb5ac91984e6c81bb1486ddc59312
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09328124B2

Reaction notes

Loading…