反应详情

温度

-80 °C

1.6M Butyllithium/hexane (150 mL, 0.24 mol, 1.09 eq) was added to a solution of 2-fluorobromobenzene (26 mL, 0.24 mol, 1.09 eq) in THF (200 mL) in a stream of argon at −90° C. The reaction mixture was cooled to −80° C., and a solution of compound tert-butyl 6-[(cyclopropylmethoxy)methyl]-6-hydroxy-1,4-oxazepane-4-carboxylate (Preparation 44, 50 mL, 0.22 mol, 1 eq) in THF was added dropwise. Then the mixture was cooled to −100° C., and a solution of borontrifluoride diethyletherate (30.4 g, 0.24 mol, 1.09 eq) in THF (300 mL) was added at this temperature for 30 min. The reaction mixture was heated to 0° C. for 5 h, and a 5M sodium hydrogen sulfate solution (50 mL) was added. The organic layer was separated and evaporated, and the residue was distributed between water and ether. The organic layer was separated, washed with water and brine, dried, and evaporated. The residue was dissolved in MeOH (200 mL). Ethylenediamine (30 mL) was added to the mixture, which was brought to boiling, cooled, evaporated, and coevaporated with dioxane. The residue was subjected to chromatography (silica gel, carbon tetrachloride→chloroform→chloroform/MeOH 19:1), evaporated, and dried to title compound (38 g, 0.12 mol, 55%).

1. temperatureThen the mixture was cooled to −100° C.
2. temperatureThe reaction mixture was heated to 0° C. for 5 h
3. customThe organic layer was separated
4. customevaporated
5. customThe organic layer was separated
6. washwashed with water and brine
7. customdried
8. customevaporated
9. dissolutionThe residue was dissolved in MeOH (200 mL)
10. additionEthylenediamine (30 mL) was added to the mixture, which
11. temperaturecooled
12. customevaporated
13. customevaporated