反应详情

(R)-8-Fluoro-5-methyloxycarbonyl-3-(N-3-pentyl-N-n-propylamino)chroman (0.72 g, 2.13 mmol) was hydrolysed with KOH (0.20 g, 3.1 mmol) in 20 ml MeOH and 10 ml H2O, under reflux conditions for 20 hours and gave after evaporation, and co-evaporation with toluene, (R)-8-fluoro-5-carboxy-3-(N-3-pentyl-N-n-propylamino)chroman as a white solid. SOCl2 (0.8 ml, 11 mmol) was added to a slurry of (R)-8-fluoro-5-carboxy-3-(N-3-pentyl-N-n-propylamino)chroman in 50 ml dry CH2Cl2 and 1 drop DMF (catalytic amount). After reflux for 2 hours, the slurry was evaporated, and the residue, dissolved in 10 ml dry THF was added dropwise to 35 ml ice-cooled conc. NH3 under stirring. The THF was evaporated after 2 hours and extraction with EtOAc×2, drying (Na2SO4) and evaporation gave 0.51 g of a crude product. Purification by flash chromatography with hexane:EtOAc:NH3, (60:40:0.5) gave 0.41 g of (R)-5-carbamoyl-8-fluoro-3-(N-3-pentyl-N-n-propylamino)chroman as light yellow crystals.

1. customgave
2. customafter evaporation, and co-evaporation with toluene, (R)-8-fluoro-5-carboxy-3-(N-3-pentyl-N-n-propylamino)chroman as a white solid
3. temperatureAfter reflux for 2 hours
4. customthe slurry was evaporated
5. dissolutionthe residue, dissolved in 10 ml dry THF
6. additionwas added dropwise to 35 ml ice-
7. temperaturecooled conc. NH3
8. customThe THF was evaporated after 2 hours
9. extractionextraction with EtOAc×2
10. customdrying
11. custom(Na2SO4) and evaporation
12. customgave 0.51 g of a crude product
13. customPurification by flash chromatography with hexane