反应详情

A mixture of 2-(3,4-dimethoxy-phenyl)-N-[3-(3,4-dimethoxy-phenyl)-propyl]-N-(1-(S)-phenyl-ethyl)-acetamide (7.0 g, 14.65 mmol) and phosphorus oxide chloride (13.4 ml, 146.5 mmol) in anhydrous acetonitrile, (160 ml) was heated at reflux for 6.5 h, under nitrogen. After cooling to RT, the volatiles were removed under vacuum and the resulting oil was dissolved in anhydrous methanol before evaporation to dryness (repeated twice). The resulting brown oil was dissolved again in anhydrous methanol (122 ml) and cooled at −78° C., under nitrogen. Then, sodium borohydride (3.02 g, 79.99 mmol) was added portionwise in 5 h to the reaction mixture kept at −78° C. The reaction was quenched by dropwise addition of aqueous 1N HCl (8 ml) and the mixture was allowed to warm to RT before the solvent was removed under vacuum and water (175 ml) was added. After extraction with CH2Cl2 (4×150 ml), the organic layer was dried over anhydrous magnesium sulfate and the solvent was removed under vacuum. The resulting crude oil was purified by flash chromatography (CH2Cl2/CH3OH: 36/1) giving the pure diastereoisomer 1-(S)-(3,4-dimethoxy-benzyl)-7,8-dimethoxy-2-(1-(S)-phenyl-ethyl)-2,3,4,5-tetrahydro-1H-benzo[c]azepine as a yellow oil (1.36 g, 20%).

1. temperaturewas heated
2. temperatureat reflux for 6.5 h, under nitrogen
3. customthe volatiles were removed under vacuum
4. dissolutionthe resulting oil was dissolved in anhydrous methanol before evaporation to dryness (
5. dissolutionThe resulting brown oil was dissolved again in anhydrous methanol (122 ml)
6. temperaturecooled at −78° C., under nitrogen
7. customkept at −78° C
8. customThe reaction was quenched by dropwise addition of aqueous 1N HCl (8 ml)
9. temperatureto warm to RT before the solvent
10. customwas removed under vacuum and water (175 ml)
11. additionwas added
12. extractionAfter extraction with CH2Cl2 (4×150 ml)
13. dry with materialthe organic layer was dried over anhydrous magnesium sulfate
14. customthe solvent was removed under vacuum
15. customThe resulting crude oil was purified by flash chromatography (CH2Cl2/CH3OH: 36/1)