反应详情

温度

85 °C

A stirred mixture of 290.0 g (1.80 mol) of 4-oxazol-4-yl-phenol (H. Jones, et al., J. Med. Chem., 21, 1110 (1978)), 737.7 g (2.70 mol) of methanesulfonic acid 2-benzyloxycarbonylamino-ethyl ester, and 746.0 g (5.40 mol) of potassium carbonate in 4.6 l of dry dimethylsulfoxide was heated to about 85° C. An additional 500 ml of dimethylsulfoxide was added and the viscous slurry was stirred at about 80° C. for about an additional two hours. The resulting mixture was cooled to about 50° C., poured into about 1 l of stirred ice water, slurried for about one hour, and then filtered. The wet filter cake was washed with water (2×1 l), and then partially dried by aspiration under vacuum for about two hours. The moist solid was charged into a round-bottomed flask, 6 l of methanol was added, and the mixture was then warmed to about 60° C. where 3 l of water was added. The heating source was removed, the mixture was stirred for about eighteen hours, and then filtered. The filter cake was washed with 2:1 methanol/water (v/v; 2×500 ml), and then dried under vacuum at about 40° C. for about eighteen hours. The title compound (389.5 g, 64% yield) was obtained as a beige powder.

1. temperatureThe resulting mixture was cooled to about 50° C.
2. waitslurried for about one hour
3. filtrationfiltered
4. washThe wet filter cake was washed with water (2×1 l)
5. custompartially dried by aspiration under vacuum for about two hours
6. additionThe moist solid was charged into a round-bottomed flask
7. addition6 l of methanol was added
8. temperaturethe mixture was then warmed to about 60° C. where 3 l of water
9. additionwas added
10. customThe heating source was removed
11. stirringthe mixture was stirred for about eighteen hours
12. filtrationfiltered
13. washThe filter cake was washed with 2:1 methanol/water (v/v; 2×500 ml)
14. customdried under vacuum at about 40° C. for about eighteen hours