N,N-Dimethylaniline → 4-Chloro-6-(trifluoromethyl)pyrimidin-2-amine
Reaction equation
O[C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([NH2:12])[N:3]=1.P(Cl)(Cl)([Cl:15])=O.CN(C)C1C=CC=CC=1>>[Cl:15][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[N:5]=[C:4]([NH2:12])[N:3]=1Participants
Procedure
33.4 g (0.186 mol) of 4-hydroxy-6-trifluoromethylpyrimidin-2-ylamine are added in portions (in each case ca. 5 g) to a mixture of 85 ml of phosphorus oxychloride and 47.5 ml of dimethylaniline and the mixture is heated at reflux until the added solid has dissolved. The mixture is then heated at reflux for a further 90 minutes. After cooling, the reaction mixture is added to ice water while observing the safety precautions for phosphorus oxychloride. The aqueous phase is extracted with methylene chloride, the organic phase is separated off and dried with sodium sulfate, and the drying agent is filtered off. Following concentration by evaporation, 47.8 g of a crude mixture are obtained. Following column chromatographic separation with ethyl acetate/heptane as eluent, 8.5 g of 4-chloro-6-trifluoromethylpyrimidin-2-ylamine were obtained (solid, 22% yield, purity 95%).
Workup
- temperaturethe mixture is heated
- temperatureat reflux until the added solid
- dissolutionhas dissolved
- temperatureThe mixture is then heated
- temperatureat reflux for a further 90 minutes
- temperatureAfter cooling
- extractionThe aqueous phase is extracted with methylene chloride
- customthe organic phase is separated off
- dry with materialdried with sodium sulfate
- filtrationthe drying agent is filtered off
- concentrationconcentration
- customby evaporation, 47.8 g of a crude mixture
- customare obtained
- customcolumn chromatographic separation with ethyl acetate/heptane as eluent
Sources & evidence
- ORD record
- ord-7ffe31f7c4734dbeb3d84deccfa01aec
- Source dataset
- uspto-grants-2013_05
- Patent number
- US08445408B2
Reaction notes
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