反应详情

TiCl3 15% in water (35 ml) was added slowly to a mixture of (±)-3-(3-chlorophenyl)-α-(4-chlorophenyl)-α-(1-methyl-1H-imidazol-5-yl)-2,1-benzisoxazole-5-methanol (prepared as described in WO 97/21701) (0.0111 mol) in THF (50 ml). The mixture was stirred at room temperature for 24 hours, basified with NaOH 3N, extracted with DCM, filtered over celite and pasted up with DCM. The organic layer was separated, dried (MgSO4), filtered and the solvent was evaporated till dryness. The residue (4.4 g) was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 96/4/0.1; 20–45 μm). Two pure fractions were collected and their solvents were evaporated, yielding 1.6 g F1 (34%) and 1 g of 2-amino-α-(3-chlorophenyl)-5-[(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl]-benzene methanol (21%). F1 was crystallized from acetonitrile and DIPE. The precipitate was filtered off, washed with diethyl ether and dried, yielding 0.8 g (16.5%) of [2-amino-5-[(4-chlorophenyl)(1-methyl-1H-imidazol-5-yl)methyl]phenyl](3-chlorophenyl)-methanone (intermediate 16), mp. 179° C.

1. extractionextracted with DCM
2. filtrationfiltered over celite
3. customThe organic layer was separated
4. dry with materialdried (MgSO4)
5. filtrationfiltered
6. customthe solvent was evaporated till dryness
7. customThe residue (4.4 g) was purified by column chromatography over silica gel (eluent: CH2Cl2/CH3OH/NH4OH 96/4/0.1; 20–45 μm)
8. customTwo pure fractions were collected
9. customtheir solvents were evaporated