反应详情

温度

70 °C

A mixture of 1-chloro-(4-fluorophenoxy)propane (2.3 g), intermediate 11 (3 g) and N,N-diethylethanamine (2.8 ml) in DMF (50 ml) was stirred for 48 hours at 70° C. The reaction mixture was cooled and the solvent was evaporated. The residue was partitioned between DCM and water. The organic layer was separated, washed with water, dried, filtered and the solvent was evaporated. The residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH 95/5). The pure fractions were collected and the solvent was evaporated. The residue was crystallized from ACN (0° C.). The precipitate was filtered off and dried (vacuum; 50° C.), yielding 1.17 g (26%) [1-[3-(4-fluorophenoxy)propyl]-4-piperidinyl]methyl 4-amino-5-chloro-2-methoxybenzoate (compound 1, mp. 140.0° C.).

1. temperatureThe reaction mixture was cooled
2. customthe solvent was evaporated
3. customThe residue was partitioned between DCM and water
4. customThe organic layer was separated
5. washwashed with water
6. customdried
7. filtrationfiltered
8. customthe solvent was evaporated
9. customThe residue was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH 95/5)
10. customThe pure fractions were collected
11. customthe solvent was evaporated
12. customThe residue was crystallized from ACN (0° C.)
13. filtrationThe precipitate was filtered off
14. customdried (vacuum; 50° C.)