反应详情

To a solution of 512 mg of (4R)-1-[5-chloro-3-(2-methoxyphenyl)-2-oxo-2,3-dihydro-1H-indol-3-yl]-4-hydroxy-N,N-dimet hyl-L-prolinamide (levorotatory isomer), which is the compound described in Preparation 3.2 (Isomer B) of Brochure No. WO01/55130 in DMF (5 ml) was added 57.1 mg of NaH under ice cooling, and the solution was stirred for 30 minutes at the same temperature. A solution of 415 mg of 2-methoxy-4-(trifluoromethoxy)benzene sulfonyl chloride in DMF (3 ml) was added, then, the solution was stirred for 30 minutes at the same temperature. To the reaction solution was added an aqueous solution of 10% K2CO3, and the resulting mixture was stirred at room temperature for 1 hour. Water and EtOAc were added, liquid separation was performed, and the aqueous layer was extracted with EtOAc. The combined organic layer was washed with water and saturated brine, then, was dried over MgSO4. The drying agent was separated by filtration, solvent was evaporated under reduced pressure. The obtained residue was purified by column chromatography (silicagel 60; mobile phase: n-hexane/EtOAc=1/2 to 1/2.5; v/v), to obtain 561 mg of the title compound (colorless amorphous).

1. customdescribed in Preparation 3.2 (Isomer B) of Brochure No
2. stirringthe solution was stirred for 30 minutes at the same temperature
3. stirringthe resulting mixture was stirred at room temperature for 1 hour
4. customliquid separation
5. extractionthe aqueous layer was extracted with EtOAc
6. washThe combined organic layer was washed with water and saturated brine
7. dry with materialwas dried over MgSO4
8. customThe drying agent was separated by filtration, solvent
9. customwas evaporated under reduced pressure
10. customThe obtained residue was purified by column chromatography (silicagel 60; mobile phase: n-hexane/EtOAc=1/2 to 1/2.5; v/v)