Sodium Hydroxide → 4-Chloro-2-cyclopentyl-6-(trifluoromethyl)pyrimidine
Reaction equation
[CH:1]1([C:6]2[N:11]=[C:10](O)[CH:9]=[C:8]([C:13]([F:16])([F:15])[F:14])[N:7]=2)[CH2:5][CH2:4][CH2:3][CH2:2]1.O=P(Cl)(Cl)[Cl:19].[OH-].[Na+]>>[Cl:19][C:10]1[CH:9]=[C:8]([C:13]([F:16])([F:15])[F:14])[N:7]=[C:6]([CH:1]2[CH2:5][CH2:4][CH2:3][CH2:2]2)[N:11]=1Participants
4
Conditions
- Temperature
- 75 °C
Procedure
2-Cyclopentyl-6-(trifluoromethyl)pyrimidin-4-ol (2.2 g, 9.47 mmol) was suspended in POCl3 (8.8 ml, 94.7 mmol) and heated to 75° C. for 2 h. After this time, the mixture was added to a chilled sodium hydroxide solution (1 M) and then extracted with ethyl acetate. The organic layer were dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The residue was purified by column chromatography (silica, hexanes/ethyl acetate) to afford the title compound (2.1 g, 90%) as a clear oil. MW=250.65. 1H NMR (CDCl3, 500 MHz) δ 7.46 (s, 1H), 3.42 (quin, J=8.2 Hz, 1H), 2.18-2.07 (m, 2H), 1.99-1.80 (m, 4H), 1.76-1.66 (m, 2H); APCI MS m/z 251 [M+H]+.