反应详情

温度

110 °C

A solution of (R)-5-(5-bromo-2-fluorophenyl)-6,6-difluoro-5,7,7-trimethyl-1,4-oxazepan-3-one (intermediate B6.1) (200 mg, 546 μmol) in dioxane (2 ml) was treated consecutively with trans-N,N′-dimethyl-1,2-cyclohexanediamine (16.0 mg, 109 μmol), copper(I)iodide (10.6 mg, 54.6 μmol), and sodium iodide (165 mg, 1.09 mmol). The reaction mixture was stirred at 110° C. for 15 hours. Following TLC the reaction was incomplete. Another amount of copper(I)iodide (10.6 mg, 54.6 μmol), trans-N,N′-dimethyl-1,2-cyclohexanediamine (16.0 mg, 109 μmol), and sodium iodide (165 mg, 1.09 mmol) was added. Stirring was continued at 110° C. during the weekend. For the workup, the reaction mixture was evaporated at reduced pressure and the residue was purified by chromatography on silica gel using a gradient of heptane/ethyl acetate=100:0 to 90:60 as the eluent. The (R)-6,6-difluoro-5-(2-fluoro-5-iodo-phenyl)-5,7,7-trimethyl-[1,4]oxazepan-3-one (217 mg, 96% yield) was obtained as light yellow viscous oil. MS (ISP): m/z=414.1 [M+H]+.

1. stirringStirring
2. customwas continued at 110° C. during the weekend
3. customFor the workup, the reaction mixture was evaporated at reduced pressure
4. customthe residue was purified by chromatography on silica gel using a gradient of heptane/ethyl acetate=100:0 to 90:60 as the eluent