反应详情

温度

65 °C

Prepare a slurry of sodium hydride (60% in mineral oil; 99 mg, 2.5 mmol) in DMF (4 mL) and heat to 65° C. Add a solution of 3-tert-butoxycarbonyl-7-chloro-6-hydroxy-2,3,4,5-tetrahydro-1H-benzo[d]azepine (250 mg, 0.84 mmol) in DMF (5 mL) dropwise and stir for 1 h. Add a solution of 4-fluorobenzyl bromide (191 mg, 1.0 mmol) in DMF (1 mL), stir at 65° C. for 1.5 h and cool to ambient temperature. Add water (1 mL) and concentrate the mixture to an oily residue. Partition the residue between EtOAc/hexane (1:1) and water. Dry the organic layer over Na2SO4, filter and concentrate in vacuo. Dissolve the residue in DCM, wash with 2N aqueous NaOH, dry the organic layer over Na2SO4, filter, and concentrate in vacuo. Purify by chromatography on silica gel eluting with hexane/EtOAc (20:1, 10:1 and 7:1) to give 3-tert-butoxycarbonyl-7-chloro-6-(4-fluorobenzyloxy)-2,3,4,5-tetrahydro-1H-benzo[d]azepine as an oil.

1. stirringstir at 65° C. for 1.5 h
2. temperaturecool to ambient temperature
3. concentrationAdd water (1 mL) and concentrate the mixture to an oily residue
4. customPartition the residue between EtOAc/hexane (1:1) and water
5. dry with materialDry the organic layer over Na2SO4
6. filtrationfilter
7. concentrationconcentrate in vacuo
8. dissolutionDissolve the residue in DCM
9. washwash with 2N aqueous NaOH
10. dry with materialdry the organic layer over Na2SO4
11. filtrationfilter
12. concentrationconcentrate in vacuo
13. customPurify by chromatography on silica gel eluting with hexane/EtOAc (20:1, 10:1 and 7:1)