反应详情

温度

23 °C

To a solution of (S)—N-(bis(4-methoxyphenyl)(phenyl)methyl)-4-(difluoromethyl)-4-(5-(diphenylmethyleneamino)-2-fluorophenyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (intermediate E8.1) (525 mg, 723 μmol) in dichloromethane (20 ml) was added at 23° C. trifluoroacetic acid (4.12 g, 2.79 ml, 36.2 mmol) and the mixture was stirred at 23° C. for 1 hour, whereupon 1 M HCl (14.5 ml, 14.5 mmol) and dioxane (40 ml) were added and the mixture was stirred vigorously at 23° C. for 60 hours. Poured into 1 M Na2CO3-solution, extracted with dichloromethane, washed the organic layer with brine and dried over Na2SO4. Removal of the solvent in vacuum left a brown oil. The residue was purified by chromatography on 5 g silica gel with dichloromethane/methanol/ammonium hydroxide 110:10:1 to give (S)-4-(5-amino-2-fluorophenyl)-4-(difluoromethyl)-5,6-dihydro-4H-1,3-oxazin-2-amine (82 mg, 316 μmol, 43.7% yield) as a light brown solid. MS (ISP): m/z=259.9 [M+H]+.

1. additionwere added
2. extractionextracted with dichloromethane
3. washwashed the organic layer with brine
4. dry with materialdried over Na2SO4
5. customRemoval of the solvent in vacuum
6. waitleft a brown oil
7. customThe residue was purified by chromatography on 5 g silica gel with dichloromethane/methanol/ammonium hydroxide 110:10:1