Acetic Acid → 2-Chloro-4-methoxy-6-methyl-pyrimidine-5-carboxylic acid methyl ester

反応式

[CH3:1][O:2][C:3]([C:5]1[C:6](Cl)=[N:7][C:8]([Cl:12])=[N:9][C:10]=1[CH3:11])=[O:4].C[O-].[Na+].C[C:18](O)=[O:19]>CO>[CH3:1][O:2][C:3]([C:5]1[C:6]([O:19][CH3:18])=[N:7][C:8]([Cl:12])=[N:9][C:10]=1[CH3:11])=[O:4]

参加物

実験手順

To a solution of 2,4-dichloro-6-methyl-pyrimidine-5-carboxylic acid methyl ester (15.3 g, 69.6 mmol) in methanol (150 mL) at 0° C. under nitrogen with magnetic stirring is added 0.5 M NaOMe in MeOH (139 mL, 69.6 mmol) in dropwise fashion over 1 h. HOAc (2 mL) is added and the reaction mixture is evaporated at reduced pressure. The resulting residue is treated with sat. NaHCO3 (100 mL) and extracted with EtOAc (120 mL×3). The combined organic layers are washed with water (75 mL) and brine (75 mL), dried over magnesium sulfate, filtered and evaporated at reduced pressure to obtain a cream-colored solid. Purification by chromatography on silica gel (1:3 ether/hexanes) affords the title compound a s a white solid (less polar of two isomeric addition products formed) and 4-chloro-2-methoxy-6-methyl-pyrimidine-5-carboxylic acid methyl ester. 2-Chloro-4-methoxy-6-methyl-pyrimidine-5-carboxylic acid methyl ester 1H NMR (CDCl3) δ=4.03 (s, 3H), 3.92 (s, 3H), 2.48 (s, 3H). 4-Chloro-2-methoxy-6-methyl-pyrimidine-5-carboxylic acid methyl ester 1H NMR (CDCl3) δ=4.03 (s, 3H), 3.95 (s, 3H), 2.50 (s, 3H).