反应详情

Add sodium triacetoxyborohydride (0.115 g, 0.543 mmol) portionwise to a solution of (S)-(3,5-bis-trifluoromethyl-benzyl)-(2-methyl-2H-tetrazol-5-yl)-(7-methyl-8-trifluoromethyl-2,3,4,5-tetrahydro-1H-benzo[b]azepin-5-yl)-amine (Example 3, Step 18) (0.200 g, 0.362 mmol), 5-formyl-2-hydroxy-benzoic acid methyl ester (0.195 g, 1.08 mmol) and glacial acetic acid (1 mL) in acetonitrile (10 mL) at room temperature under an atmosphere of nitrogen and stir for 24 h. Quench the reaction with saturated sodium bicarbonate (5 mL) and dilute with dichloromethane (15 mL). Separate the layers and wash the organic layer with saturated sodium bicarbonate and brine (20 mL each). Dry the organic layer over sodium sulfate, filter and remove the solvent under reduced pressure. Purify the residue using flash column chromatography on silica gel, eluting with hexanes/ethyl acetate (80:20), to provide the title compound as an off-white foam (0.155 g, 60%). 1H NMR (CDCl3, 300 MHz) δ 10.63 (s, 1H), 7.89 (s, 1H), 7.67 (s, 1H), 7.56 (m, 2H), 7.28 (s, 1H), 6.96 (m, 2H), 5.56 (m, 1H), 4.85-4.98 (m, 2H), 4.14 (s, 3H), 3.89 (s, 3H), 2.95-3.00 (m, 1H), 2.73-2.80 (m, 1H), 2.30 (s, 3H), 2.00-2.13 (m, 2H), 1.43-1.72 (m, 2H), 1.21-1.34 (m, 3H); ESI MS m/z 717 [C32H29F9N6O3+H]+.

1. customQuench
2. customthe reaction with saturated sodium bicarbonate (5 mL)
3. customSeparate the layers
4. washwash the organic layer with saturated sodium bicarbonate and brine (20 mL each)
5. dry with materialDry the organic layer over sodium sulfate
6. filtrationfilter
7. customremove the solvent under reduced pressure
8. customPurify the residue
9. washeluting with hexanes/ethyl acetate (80:20)