[F:1][C:2]1([F:22])[CH2:7][O:6][C:5]([NH2:8])=[N:4][C@@:3]1([C:10]1[CH:15]=[C:14]([N+:16]([O-:18])=[O:17])[C:13]([O:19]C)=[CH:12][C:11]=1[F:21])[CH3:9].B(Br)(Br)Br>ClCCl>[NH2:8][C:5]1[O:6][CH2:7][C:2]([F:1])([F:22])[C@:3]([C:10]2[C:11]([F:21])=[CH:12][C:13]([OH:19])=[C:14]([N+:16]([O-:18])=[O:17])[CH:15]=2)([CH3:9])[N:4]=1A solution of (R)-5,5-difluoro-4-(2-fluoro-4-methoxy-5-nitro-phenyl)-4-methyl-5,6-dihydro-4H-[1,3]oxazin-2-ylamine (intermediate A6.11) (558 mg, 1.75 mmol) in dichloromethane (16 ml) was cooled to 0° C. and treated with a solution of boron tribromide in dichloromethane (1M, 2.62 ml). After stirring at room temperature for 2 hours, the reaction mixture was diluted with dichloromethane, then extracted with water (3 ml). The organic layer was separated, dried over sodium sulphate and evaporated. The crude product was purified by flash chromatography on silica gel using a gradient of hexane/ethyl acetate=100:0 to 0:100 as the eluent. The 4-((R)-2-amino-5,5-difluoro-4-methyl-5,6-dihydro-4H-[1,3]oxazin-4-yl)-5-fluoro-2-nitro-phenol (intermediate F2.1) (300 mg, 56% yield) was obtained as a brown solid. MS (ISP): m/z=457.3 [M+H]+.
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