反应详情

In a round-bottom flask, NaH 60% dispersion in mineral oil (3.07 g, 77 mmol) was washed 2× with hexane and suspended in DMF. Then 2-amino-5-acetyl-4-methyl-thiazole (10.0 g , 64 mmol) was added and stirred while cooling in an ice bath. Stirring continued until the NaH was consumed. Diphenyl carbonate (34 g, 160 mmol) was added while cooling and after the addition was complete the reaction mixture was stirred for an additional ˜30 minutes at room temperature. The dimethylformamide was removed on a rotary evaporator (high vacuum, 40° C.) to yield a brown residue. This residue was dissolved in 1 L of chloroform and washed successively with 2 L of 0.5N aqueous hydrochloric acid, twice with 1 L of water, and finally by 1 L of brine. The aqueous portions were back extracted twice with 300 mL of chloroform. The combined organic fractions were dried over anhydrous sodium sulfate, filtered and concentrated on a rotary evaporator to give a white solid. This was chromatographed on silica (15%-70% EtOAc/hexane) to give 15 g of the desired carbamate as a white solid. 1H NMR (300 MHz, CDCl3) δ: 11.42 (bs, 1H), 7.47-7.40 (m, 2H), 7.33-7.27 (m, 1H), 7.22-7.18 (m, 2H), 2.72 (s, 3H), 2.50 (s, 3H). ESI MS: (M+H)+=277.1.

1. temperaturewhile cooling in an ice bath
2. stirringStirring
3. customwas consumed
4. temperaturewhile cooling
5. additionafter the addition
6. stirringwas stirred for an additional ˜30 minutes at room temperature
7. customThe dimethylformamide was removed on a rotary evaporator (high vacuum, 40° C.)
8. customto yield a brown residue
9. washwashed successively with 2 L of 0.5N aqueous hydrochloric acid, twice with 1 L of water
10. extractionThe aqueous portions were back extracted twice with 300 mL of chloroform
11. dry with materialThe combined organic fractions were dried over anhydrous sodium sulfate
12. filtrationfiltered
13. concentrationconcentrated on a rotary evaporator
14. customto give a white solid
15. customThis was chromatographed on silica (15%-70% EtOAc/hexane)