反应详情

A 4.26 g portion of 1,1′-carbonyldiimidazole was added to 5.00 g of (S)-1-phenyl-1,2,3,4-tetrahydroisoquinoline and 25 ml of toluene and stirred at room temperature for 30 minutes. By adding 25 ml of water thereto, the water layer was separated, the organic layer was washed with 25 ml of water, and the solvent was evaporated under a reduced pressure. A 10 ml portion of toluene was added to the residue. This solution was added dropwise at room temperature to a solution prepared by adding 1.00 g of sodium hydride to a mixture of 3.65 g of (R)-quinuclidin-3-ol, 25 ml of toluene and 5 ml of DMF and heating to 100° C., and 5 ml of toluene was further added thereto. This was heated at 110° C. for 3 hours, cooled and mixed with 25 ml of water, and the water layer was separated. This was again washed with 25 ml of water, and the organic layer was extracted with a mixture of 3.25 g of concentrated hydrochloric acid and 18 ml of water. 34 ml of EtOAc, and a mixture of 5.28 g of potassium carbonate and 14 ml of water were added to the thus obtained water layer, the thus obtained organic layer was washed with 7 ml of water, and then the solvent was evaporated under a reduced pressure to obtain solifenacin.

1. customthe water layer was separated
2. washthe organic layer was washed with 25 ml of water
3. customthe solvent was evaporated under a reduced pressure
4. additionA 10 ml portion of toluene was added to the residue
5. additionThis solution was added dropwise at room temperature to a solution
6. customprepared
7. temperatureheating to 100° C.
8. temperatureThis was heated at 110° C. for 3 hours
9. temperaturecooled
10. customthe water layer was separated
11. washThis was again washed with 25 ml of water
12. extractionthe organic layer was extracted with a mixture of 3.25 g of concentrated hydrochloric acid and 18 ml of water
13. addition34 ml of EtOAc, and a mixture of 5.28 g of potassium carbonate and 14 ml of water
14. additionwere added to the thus obtained water layer
15. washthe thus obtained organic layer was washed with 7 ml of water
16. customthe solvent was evaporated under a reduced pressure