反应详情

温度

-1 °C

Distilled 5-(hydroxymethyl)thiazole (14.1 g, 123 mmol) and triethylamine (17.9 mL, 129 mmol) were dissolved in ethyl acetate (141 mL) and cooled to -1° C. (ice/salt bath). A solution of 4-nitrophenyl chloroformate (26.0 g, 129 mmol) dissolved in ethyl acetate (106 mL) was added dropwise over 50 minutes at an internal temperature of 0°-4° C. An ethyl acetate flask rinse (20 mL) was also added. Salts precipitated from solution throughout the addition. The yellow mixture was stirred another 1 hour 45 minutes at 0°-2°C., then a solution of dilute HCl (3.1 g, 31 mmol of conc. HCl in 103 mL water) was added at once. The mixture was stirred for 0.5 hours while warming to 15° C., then stirring was stopped. The organic layer was washed twice with aqueous 5% K2CO3 solution (2×70 mL), then dried with Na2SO4 (30 g). After filtration the solution was concentrated under vacuum on a rotary evaporater (bath temperature of 41° C.) to a brown oil (38 g). The crude 5-(p-nitrophenyoxycarbonyloxymethyl)-thiazole was dissolved in ethyl acetate (282 mL), then cooled in an ice bath to 2° C. Dry HCl gas (7.1 g, 195 mmol) was bubbled in slowly over 50 minutes (temperature 2°-4° C.). After stirring for another 1 hour 45 minutes at 2°-4° C., the solid precipitate was collected on a sintered glass funnel under a nitrogen blanket and the flask was washed out with 50 mL cold ethyl acetate which was used to rinse the filter cake. The cake was dried on the funnel under strong nitrogen purge for 15 minutes then dried in a vacuum oven at 50° C. with a nitrogen purge to provide 29.05 g of the title compound as tan powder, mp. 131°-135° C. (dec.). 1H NMR (DMSO-d6) δ9.21 (d, 1H), 8.27 (m, 2H), 8.06 (d, 1H), 7.52 (m, 2H), 5.54 (s, 2H). 13C NMR (DMSO-d6) δ157.3, 155.2, 151.8, 145.3, 143.7, 131.9, 125.5, 122.7, 62.1.

1. additionwas added dropwise over 50 minutes at an internal temperature of 0°-4° C
2. washAn ethyl acetate flask rinse (20 mL)
3. additionwas also added
4. customSalts precipitated from solution throughout the addition
5. stirringThe mixture was stirred for 0.5 hours
6. temperaturewhile warming to 15° C.
7. stirringstirring
8. washThe organic layer was washed twice with aqueous 5% K2CO3 solution (2×70 mL)
9. dry with materialdried with Na2SO4 (30 g)
10. filtrationAfter filtration the solution
11. concentrationwas concentrated under vacuum on a rotary evaporater (bath temperature of 41° C.) to a brown oil (38 g)
12. dissolutionThe crude 5-(p-nitrophenyoxycarbonyloxymethyl)-thiazole was dissolved in ethyl acetate (282 mL)
13. temperaturecooled in an ice bath to 2° C
14. stirringAfter stirring for another 1 hour 45 minutes at 2°-4° C.
15. customthe solid precipitate was collected on a sintered glass funnel under a nitrogen blanket
16. washthe flask was washed out with 50 mL cold ethyl acetate which
17. washto rinse the filter cake
18. customThe cake was dried on the funnel under strong nitrogen
19. custompurge for 15 minutes
20. customthen dried in a vacuum oven at 50° C. with a nitrogen
21. custompurge