反应详情

温度

-78 °C

A mixture of the title compound (1.0388 g, 2.8 mmol) from Example 98, Step A, and Pd/C (0.28 g) in EtOH/EtOAc (80 ml) was hydrogenated with a balloon for 30 min. The mixture was filtered and the solvent was evaporated. To a solution of the residue and dibromomethane (0.43 ml, 6.16 mmol) in THF (20 ml) at -78° C. for 10 min, was added dropwise a freshly prepared solution of lithium tetramethylpiperidine (6.16 mmol) in THF (10 ml) at 0° C. over 10 min. The mixture was stirred at -78° C. for 10 min. A newly prepared lithium hexamethyldisilazane (5.6 mmol) in THF (10 ml) at 0° C. was added dropwise in 5 min to the mixture at -78° C. The mixture was then slowly warmed to 0° C. in an ice-bath for 30 min. n-BuLi (10.5 ml, 16.8 mmol, 1.6M) was added slowly over 10 min. The mixture was stirred at 0° C. for 5 min and warmed to room temperature for 45 min. The color of the solution changed from yellow to brown. The mixture was then cooled to -78° C. and quenched into a stirred solution of acidic ethanol (30 ml) dropwise at 0° C. over 30 min. The solution was diluted with EtOAc (200 ml) and washed with 1N HCl (30 ml). The aqueous was extracted with EtOAc (2×30 ml). The combined EtOAc layers were washed with brine, and dried over sodium sulfate. The title compound was obtained in 48% yield (0.522 g) as a colorless oil by flash column (EtOAc:hexane=1:9).

1. filtrationThe mixture was filtered
2. customthe solvent was evaporated
3. additionwas added slowly over 10 min
4. stirringThe mixture was stirred at 0° C. for 5 min
5. temperaturewarmed to room temperature for 45 min
6. temperatureThe mixture was then cooled to -78° C.
7. customquenched into a stirred solution of acidic ethanol (30 ml) dropwise at 0° C. over 30 min
8. additionThe solution was diluted with EtOAc (200 ml)
9. washwashed with 1N HCl (30 ml)
10. extractionThe aqueous was extracted with EtOAc (2×30 ml)
11. washThe combined EtOAc layers were washed with brine
12. dry with materialdried over sodium sulfate