反应详情

A solution of cyclopentanone (26.2 μl, 296 μmol) and (S)-4-(5-amino-2-fluoro-phenyl)-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine (intermediate A8.4) (60 mg, 269 μmol) in dichloromethane (2 ml) was treated with acetic acid (30.8 μl, 538 μmol) followed by sodium triacetoxyborohydride (85.4 mg, 403 μmol). The reaction mixture was stirred at room temperature for 2.5 hours. For the workup, the reaction mixture was quenched with a saturated solution of sodium hydrogencarbonate, then extracted with ethyl acetate. The organic layer was washed twice with water, dried over sodium sulphate, and evaporated at reduced pressure. The crude product was purified by chromatography on a silica-NH2 phase using a gradient of n-hexane/ethyl acetate=50:50 to 0:100 as the eluent to yield the (S)-4-(5-cyclopentylamino-2-fluoro-phenyl)-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine (5 mg, 6% yield). MS (ISP): m/z=292.1 [M+H]+.

1. customFor the workup, the reaction mixture was quenched with a saturated solution of sodium hydrogencarbonate
2. extractionextracted with ethyl acetate
3. washThe organic layer was washed twice with water
4. dry with materialdried over sodium sulphate
5. customevaporated at reduced pressure
6. customThe crude product was purified by chromatography on a silica-NH2 phase