反应详情

Dissolve 1-Benzhydryl-azetidin-3-ol (250 mg, 1.04 mmoL) in methanol (3.0 mL) and add to Pd(OH)2 (50 mg) under nitrogen. Degas reaction vessel and purge with 60 psi H2 (g). Repeat degass/H2 purge cycle again. Allow to stir under 60 psi H2 for 15 h. Release reaction and filter through celite with additional methanol. Evaporate methanol to yield azetidin-3-ol as a liquid which is used without further purification. Combine 4-(3-Phenyl-indole-1-sulfonyl)-benzoic acid (200 mg, 0.53 mmol) and azetidin-3-ol (50 mg, 0.68 mmol, excess) in dichloromethane (1.0 mL) and triethylamine (0.500 mL, 3.58 mmol, excess) and add benzotriazol-1-yloxytris(dimethylamino)phosphonium hexfluorophosphate (BOP Reagent) (300 mg, 0.66 mmol, excess) at room temperature. Stir for 30 minutes, load entire reaction directly onto pre-packed silica gel column and purify by flash column chromatography (EtOAc/Hexanes) to yield 167 mg of (3-Hydroxy-azetidin-1-yl)-[4-(3-phenyl-indole-1-sulfonyl)-phenyl]-methanone as a white foam (73%). LRMS: MH+ 432.97.

1. customis used without further purification
2. customload entire reaction directly onto pre-packed silica gel column
3. custompurify by flash column chromatography (EtOAc/Hexanes)