反应详情

温度

60 °C

Triphenylphosphine (0.157 mg, 0.60 mmol) was added to a stirred solution of N-{1-[2-(azidomethyl)-4-chlorophenyl]-2,2,2-trifluoroethyl}-N-(4-methoxyphenyl)amine (0.199 mg, 0.538 mmol) in water (1 mL) and water (30 μL). After 16 h the volatiles were evaporated in vacuo, the residue was dissolved in methanol (1 mL), potassium hydroxide (1 pellet) was added and the mixture was stirred at 60° C. for 15 min. The reaction mixture was then cooled and partitioned between ether and water. The organic layer was dried (Na2SO4) and evaporated to a gum. EDC (154.7 mg, 0.81 mmol) was added to a stirred mixture of this crude amine, N-Boc-L-proline (115.8 mg, 0.54 mmol) and HOAT (36.6 mg, 0.27 mmol) in DMF (3 mL). After 16 h, the mixture was concentrated and the residue was partitioned between EtOAc and 10% NaHCO3 solution. The organic layer was washed with water and brine, dried (Na2SO4) and evaporated to a gum. This was purified by chromatography on silica gel (eluting with EtOAc/CHCl3, 1:5) to give N-(5-chloro-2-{1-[(4-methoxyphenyl)amino]-2,2,2-trifluoroethyl}benzyl)-1-(tert-butoxycarbonyl)-L-prolinamide (196 m g) as a glass: MS: 542.3 (M+1).

1. customAfter 16 h the volatiles were evaporated in vacuo
2. dissolutionthe residue was dissolved in methanol (1 mL)
3. additionpotassium hydroxide (1 pellet) was added
4. temperatureThe reaction mixture was then cooled
5. custompartitioned between ether and water
6. dry with materialThe organic layer was dried (Na2SO4)
7. customevaporated to a gum
8. waitAfter 16 h
9. concentrationthe mixture was concentrated
10. customthe residue was partitioned between EtOAc and 10% NaHCO3 solution
11. washThe organic layer was washed with water and brine
12. dry with materialdried (Na2SO4)
13. customevaporated to a gum
14. customThis was purified by chromatography on silica gel (eluting with EtOAc/CHCl3, 1:5)