Dichloromethane → 4-{[2-Chloro-4-(trifluoromethyl)pyrimidin-5-yl]carbonyl}morpholine

HRID 38768

Reaction equation

[Cl:1][C:2]1[N:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[C:5]([C:12](Cl)=[O:13])=[CH:4][N:3]=1.ClCCl.[NH:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1.C(N(CC)CC)C>O.C(OCC)(=O)C>[Cl:1][C:2]1[N:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[C:5]([C:12]([N:18]2[CH2:23][CH2:22][O:21][CH2:20][CH2:19]2)=[O:13])=[CH:4][N:3]=1

Participants

Conditions

Temperature: -70 °C

Procedure

A mixture of 2-chloro-4-(trifluoromethyl)pyrimidine-5-carbonyl chloride (2.8 g) and dichloromethane (56 mL) was cooled in a dry ice-acetone bath, and morpholine (990 μL) and triethylamine (1.9 mL) were added dropwise thereto while keeping the temperature at −50° C. or lower. The reaction mixture was stirred at −70° C. for 2.5 hours, and then ethyl acetate and water were added thereto. The aqueous layer was extracted with ethyl acetate, and the organic layer was washed with water and saturated brine. After drying over anhydrous magnesium sulfate, the solvent was evaporated under reduced pressure and the obtained residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate) to obtain 4-{[2-chloro-4-(trifluoromethyl)pyrimidin-5-yl]carbonyl}morpholine (2.8 g) as a white solid.

Workup

temperaturewas cooled in a dry ice-acetone bath
customat −50° C.
extractionThe aqueous layer was extracted with ethyl acetate
washthe organic layer was washed with water and saturated brine
dry with materialAfter drying over anhydrous magnesium sulfate
customthe solvent was evaporated under reduced pressure
customthe obtained residue was purified by silica gel column chromatography (eluent: hexane-ethyl acetate)

Sources & evidence

ORD record: ord-67953608ec5b4129a0de88b6f59f7c5b
Source dataset: uspto-grants-2013_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08524727B2

Linked notes

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