反应详情

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).

1. customthe reaction mixture is evaporated at reduced pressure
2. additionThe resulting residue is treated with sat. NaHCO3 (100 mL)
3. extractionextracted with EtOAc (120 mL×3)
4. washThe combined organic layers are washed with water (75 mL) and brine (75 mL)
5. dry with materialdried over magnesium sulfate
6. filtrationfiltered
7. customevaporated at reduced pressure
8. customto obtain a cream-colored solid
9. customPurification by chromatography on silica gel (1:3 ether/hexanes)