Sodium hydride → 1-(1-benzhydryl-azetidin-3-ylmethyl)-6-fluoro-1H-indole

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

To a suspension of sodium hydride (60% mineral oil dispersion, 0.19 g, 4.6 mmol) in anhydrous DMF (20 mL) was added 6-fluoroindole (0.65. g, 2.6 mmol) at 0° C. The mixture was stirred at 0° C. for 30 minutes, then a solution of methanesulfonic acid 1-benzhydryl-azetidine-3-ylmethyl ester (0.78 g, 2.3 mmol) in DMF was introduced at 0° C. The resulting mixture heated at 60° C. for 16 hours. The reaction was quenched with water and extracted with methylene chloride (3×50 mL). The organic layer was washed with water (3×50 mL), dried over anhydrous sodium sulfate, filtered and the solvent removed under vacuum. The crude oil was column chromatographed on silica gel (10-30% ethyl acetate-hexane). The product-containing fractions were concentrated under vacuum to give 0.60 g (52%) of the title compound as a light brown oil. MS ES m/e 371 (M+H)+; 1H NMR (500 MHz, DMSO-D6): 2.76-2.79 δ (m, 3H), 3.05-3.07 δ (m, 2H), 4.29-4.31 δ (m, 3H), 6.37 δ (m, 1H), 6.78-6.83 δ (m, 1H), 7.09-7.13 δ (m, 2H), 7.18-7.22 δ (m, 4H), 7.31-7.35 δ (m, 6H), 7.46 δ (m, 1H).

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