反应详情

Under nitrogen atmosphere, to a solution of 280 mg of the compound obtained in Step 118-6 in CHCl3 (2.8 ml) was added sequentially 107 mg of methanesulfonic acid anhydride and Et3N (104 mg), then, the reaction mixture was stirred for 30 minutes under the same condition. Under nitrogen atmosphere, to a suspension of (4R)-4-hydroxy-N,N-dimethyl-L-prolinamide trifluoroacetate (2.57 mmol) in CHCl3 (5 ml) was added Et3N (520 mg) under dry ice-acetone cooling. To the reaction solution was added dropwise over 30 seconds the reaction solution of the mesyl form prepared above, then the reaction mixture was warmed to room temperature over two hours. To the reaction solution was added water and CHCl3, liquid separation was performed, and the aqueous layer was extracted with CHCl3. The combined organic layer was washed with saturated brine, dried over MgSO4, then, the drying agent was separated by filtration and the filtrate was concentrated. The obtained residue was separated and purified by column chromatography (silicagel 60; mobile phase: CHCl3/MeOH/NH4OH=95/5/0.5; v/v/v) to obtain respectively 33 mg (Isomer A: brown amorphous) and 24 mg (Isomer B: pale brown amorphous) of two species of diastereoisomers of the title compound.

1. customprepared above
2. additionTo the reaction solution was added
3. customwater and CHCl3, liquid separation
4. extractionthe aqueous layer was extracted with CHCl3
5. washThe combined organic layer was washed with saturated brine
6. dry with materialdried over MgSO4
7. customthe drying agent was separated by filtration
8. concentrationthe filtrate was concentrated
9. customThe obtained residue was separated
10. custompurified by column chromatography (silicagel 60