(Diethylamino)sulfur trifluoride → 4-Chloro-6-(fluoromethyl)-5-methylpyrimidine

HRID 2401216Notes

Reaction equation

CCN(S(F)(F)[F:7])CC.[Cl:10][C:11]1[N:16]=[CH:15][N:14]=[C:13]([CH2:17]O)[C:12]=1[CH3:19]>ClCCl>[Cl:10][C:11]1[C:12]([CH3:19])=[C:13]([CH2:17][F:7])[N:14]=[CH:15][N:16]=1

Participants

Conditions

Temperature: -78 °C

Procedure

DAST (1.5 mL, 11.35 mmol) was added to dichloromethane (DCM) (64 mL), cooled to −78° C. and treated dropwise with a solution of (6-chloro-5-methyl-4-pyrimidinyl)methanol (Intermediate 50, 1.70 g, 10.72 mmol) in DCM (24 mL) under argon. The resulting mixture was allowed to warm to room temperature and stirred for 3 hours. The reaction was quenched by adding water (45 ml) and extracted with DCM (×2). The DCM layers were separated, combined, dried under magnesium sulfate and evaporated under reduced pressure. The residue was purified by column chromatography (SP4, 40+M) eluting with a gradient of 0-50% ethyl acetate and iso-hexane. Product containing fractions were combined and evaporated under reduced pressure to give the title compound as a yellow oil (1.29 g) m/z (ES+) 161 (M+1), title compound is 42% pure by LCMS. Also contains 4-bromo-6-(fluoromethyl)-5-methylpyrimidine, m/z (ES+) 205, 207 (M+1) (44% by LCMS)

Workup

temperatureto warm to room temperature
customThe reaction was quenched
additionby adding water (45 ml)
extractionextracted with DCM (×2)
customThe DCM layers were separated
customdried under magnesium sulfate
customevaporated under reduced pressure
customThe residue was purified by column chromatography (SP4, 40+M)
washeluting with a gradient of 0-50% ethyl acetate and iso-hexane
additionProduct containing fractions
customevaporated under reduced pressure

Sources & evidence

ORD record: ord-0ac1a5344e2f4ebe9549d288aed52367
Source dataset: uspto-grants-2014_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08796283B2

Reaction notes

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