反应详情

A mixture of 3-amino-5-chloro-1-methyl-2(1H)-pyrazinone (11.17 g, 0.070 mol) in anhydrous N,N-dimethylformamide (90 mL) was treated with oil-free sodium hydride (3.4 g, 0.154 mol). After stirring at room temperature for 1 hour, the mixture was cooled with the aid of a dry ice-acetone bath while a solution of diphenyl carbonate (16.49 g, 0.077 mol) in N,N-dimethylformamide (60 mL) was added as rapidly as possible. A wet ice bath was substituted for the dry ice bath, and the reaction mixture was stirred at approximately 0° C. for 3 hours. The mixture was allowed to briefly warm to room temperature, and was then poured into a stirred mixture of ice (350 g), concentrated hydrochloric acid (42 mL); dichloromethane (318 mL), and tetrahydrofuran (32 mL). The layers were separated, and the aqueous layer was extracted with 10:1 dichloromethane-tetrahydrofuran (5×100 mL). The combined organic solutions were dried (Na2SO4), and the solvent was rotary evaporated. After the residue was taken up in toluene, further rotary evaporation left a tan solid. This solid was taken up in dichloromethane, absorbed onto silica gel and then chromatographed using a 5:1 mixture of dichloromethane-ether as eluant. Rotary evaporation of the appropriate fractions left 9.70 g of phenyl (6-chloro-3,4-dihydro-4-methyl-3-oxopyrazin-2-yl)carbamate as a crystalline solid melting at 175°-177° C.

1. additionwas added as rapidly as possible
2. stirringthe reaction mixture was stirred at approximately 0° C. for 3 hours
3. temperatureto briefly warm to room temperature
4. customThe layers were separated
5. extractionthe aqueous layer was extracted with 10:1 dichloromethane-tetrahydrofuran (5×100 mL)
6. dry with materialThe combined organic solutions were dried (Na2SO4)
7. customfurther rotary evaporation
8. waitleft a tan solid
9. customabsorbed onto silica gel
10. customchromatographed
11. additiona 5:1 mixture of dichloromethane-ether as eluant
12. customRotary evaporation of the appropriate fractions
13. waitleft 9.70 g of phenyl (6-chloro-3,4-dihydro-4-methyl-3-oxopyrazin-2-yl)carbamate as a crystalline solid melting at 175°-177° C.