反应详情

温度

0 °C

To 5-tert-Butyl-indan-1-one (15.7 g, 83.4 mmol) in dichloromethane (150 mL) was added methanesulfonic acid (100 mL) and the resulting mixture was cooled to 0° C. Then sodium azide (10.83 g, 2 eq) was added carefully portion-wise over 15 minutes. The resulting mixture was stirred at 0° C. for about 2.5 hours. TLC analysis confirmed that all of the 5-tert-Butyl-indan-1-one had been consumed. With stirring at 0° C. was added very carefully a solution of aqueous sodium hydroxide (20%) until pH=14. Then added dichloromethane (1000 mL) and water (500 mL) which results in a large emulsion. The layers were separated and the aqueous layer was further extracted with dicholormethane (2×200 mL). Finally the combined dichloromethane layers were washed with brine (9×200 mL), dried over magnesium sulfate and filtered through a bed of celite. After concentrating and pumping to dryness there was 13.5 g of crude product as a tan solid. Purification on a 400 g Analogix Column eluting with a gradient of 10% to 60% ethyl acetate in hexane provided the correct isomer as a white powder (7.22 g) ((M+H)+=204) and the undesired isomer (1.555 g) as a white powder.

1. customhad been consumed
2. stirringWith stirring at 0° C.
3. additionwas added very carefully a solution of aqueous sodium hydroxide (20%) until pH=14
4. customThen added dichloromethane (1000 mL) and water (500 mL) which results in a large emulsion
5. customThe layers were separated
6. extractionthe aqueous layer was further extracted with dicholormethane (2×200 mL)
7. washFinally the combined dichloromethane layers were washed with brine (9×200 mL)
8. dry with materialdried over magnesium sulfate
9. filtrationfiltered through a bed of celite
10. concentrationAfter concentrating
11. customPurification on a 400 g Analogix Column
12. washeluting with a gradient of 10% to 60% ethyl acetate in hexane