反应详情

温度

-78 °C

A solution of ethylmagnesium bromide in tetrahydrofuran (1.0M, 8.90 mL, 8.90 mmol, 1.10 equiv) was added by syringe to a solution of (7S,10R)-7,8,9,10-tetrahydro-2,9,9-trimethoxy-7-methyl-10-phenanthridinol (15, 2.46 g, 8.10 mmol, 1 equiv) in tetrahydrofuran (5 mL) at -78° C. The reaction flask was transferred to an ice bath for 10 min, then was cooled to -78° C. A 100-mL flame-dried Schlenk-type flask was charged with sodium hydride (1.17 g, 48.7 mmol, 6.00 equiv) and N,N-dimethylformamide (20 mL) was added slowly over 5 min. The resulting slurry was cooled to 0° C. and ethanethiol (1.80 mL, 24.3 mmol, 3.00 equiv) was added dropwise over 15 min by syringe, causing a vigorous exotherm. After the exotherm had subsided, the slurry was warmed to 23° C. and was stirred at that temperature for 10 min. The tetrahydrofuran solution of the magnesium alkoxide prepared above was added to the slurry via cannula over 5 min. Tetrahydrofuran was then removed in vacuo and the reaction mixture was heated at reflux for 1.5 h. The resulting thick brown slurry was cooled to 23° C. and was partitioned between saturated aqueous ammonium chloride solution (500 mL) and ethyl acetate (500 mL). The aqueous layer was separated and extracted further with ethyl acetate (500 mL) and 20% methanol in dichloromethane (500 mL). The aqueous layer was neutralized by the addition of aqueous hydrochloric acid solution (1% v/v, 400 mL) and was extracted with ethyl acetate (2×500 mL). The combined organic layers were dried over sodium sulfate and were concentrated in vacuo. The residue was purified by flash column chromatography (2.5% methanol-dichloromethane initially, grading to 5% methanol-dichloromethane) to afford (7S,10R)-7,8,9,10-tetrahydro-9,9-dimethoxy-7-methyl-2,10-phenanthridinediol (16) as a yellow solid (1.66 g, 71%). ##STR26##

1. customA 100-mL flame-dried Schlenk-type flask
2. additionwas added slowly over 5 min
3. temperatureThe resulting slurry was cooled to 0° C.
4. temperaturethe slurry was warmed to 23° C.
5. additionabove was added to the slurry via cannula over 5 min
6. customTetrahydrofuran was then removed in vacuo
7. temperaturethe reaction mixture was heated
8. temperatureat reflux for 1.5 h
9. temperatureThe resulting thick brown slurry was cooled to 23° C.
10. customwas partitioned between saturated aqueous ammonium chloride solution (500 mL) and ethyl acetate (500 mL)
11. customThe aqueous layer was separated
12. extractionextracted further with ethyl acetate (500 mL) and 20% methanol in dichloromethane (500 mL)
13. additionThe aqueous layer was neutralized by the addition of aqueous hydrochloric acid solution (1% v/v, 400 mL)
14. extractionwas extracted with ethyl acetate (2×500 mL)
15. dry with materialThe combined organic layers were dried over sodium sulfate
16. concentrationwere concentrated in vacuo
17. customThe residue was purified by flash column chromatography (2.5% methanol-dichloromethane initially