反应详情

Difluoro-(4-nitro-phenyl)-acetic acid ethyl ester (compound 32.1) is reacted according to Sato, K. et. al. Chem. Pharm. Bull. 1999, 47, 1013). Briefly, compound 32.1 and catalytic Pd/C in EtOAc are placed under an atmosphere of hydrogen for 3 hours. The reaction mixture is filtered, concentrated and taken on crude to the next reaction. The crude compound, dichloromethane, 3-(trifluoromethyl)benzoyl chloride and DIEA are stirred at room temperature for 10 minutes. Water is added after which the mixture partitioned between EtOAc and water. The organic layer is separated, washed with brine, dried, filtered and concentrated under reduced pressure. Purification by flash column chromatography on silica gel using a gradient of EtOAc/hexanes provides difluoro-[4-(3-trifluoromethyl-benzoylamino)-phenyl]-acetic acid ethyl ester (compound 32.2).

1. filtrationThe reaction mixture is filtered
2. concentrationconcentrated
3. customtaken on crude to the next reaction
4. custompartitioned between EtOAc and water
5. customThe organic layer is separated
6. washwashed with brine
7. customdried
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customPurification by flash column chromatography on silica gel using a gradient of EtOAc/hexanes