反应详情

温度

0 °C

To a stirred solution of the product of step (d) (20 g) in dry tetrahydrofuran (500 mL) at 0° C. was added sodium hydride (60% dispersion in mineral oil, 2.43 g) portionwise. The reaction was stirred at 0° C. for 30 minutes then ethyl bromoacetate (8.19 g) was added dropwise and the reaction was allowed to warm to 20° C. and stirred for a further 3 hours. Ethanol (100 mL) was then added and stirring was continued at 20° C. for 30 minutes. Sodium hydroxide solution (2M, 100 mL) was then added and the resulting mixture was stirred at 20° C. for 2 hours. The reaction mixture was then partitioned between dichloromethane (700 mL) and water (700 mL). The aqueous layer was acidified to pH 1 by the addition of hydrochloric acid (2M) and then extracted with dichloromethane (3×500 mL). The combined organic layers were dried and the solvent removed in vacuo. Purification by chromatography on silica gel (Biotage), eluting with 10% methanol/1% ammonia (specific gravity 0.880) in dichloromethane gave the title compound as a pale yellow oil (15 g). LC retention time 2.18 mins. Mass spectrum m/z 485 [M+]

1. temperatureto warm to 20° C.
2. stirringstirred for a further 3 hours
3. stirringstirring
4. waitwas continued at 20° C. for 30 minutes
5. stirringthe resulting mixture was stirred at 20° C. for 2 hours
6. customThe reaction mixture was then partitioned between dichloromethane (700 mL) and water (700 mL)
7. additionThe aqueous layer was acidified to pH 1 by the addition of hydrochloric acid (2M)
8. extractionextracted with dichloromethane (3×500 mL)
9. customThe combined organic layers were dried
10. customthe solvent removed in vacuo
11. customPurification by chromatography on silica gel (Biotage)
12. washeluting with 10% methanol/1% ammonia (specific gravity 0.880) in dichloromethane