3-(1-((Tert-butoxy)carbonyl)piperidin-4-yl)propanoic acid → HCID 19081835, compound

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Reaction Conditions

Reaction Steps

3-[1-(tert-Butoxycarbonyl)piperidin-4-yl]propionic acid (4.6 g, 18 mmol), prepared as in Example 1, was dissolved in HMPA (10 mL) and THF (10 mL), and this solution was added to a -20° solution of lithium diisopropylamide (60 mmol). The mixture was warmed to 0° C., stirred for 30 minutes, and then cooled to -40° C. N-Methoxy-N-methyl-4-amino-5-chloro-2-methoxybenzamide (4.9 g, 20 mmol), prepared as in Example 2, was dissolved in HMPA (10 mL) and THF (10 mL) and this solution was added to the mixture. The mixture was allowed to warm to 0° C. over 1 hour, then diluted with water, washed with ether, acidified with hydrochloric acid, and extracted into methylene chloride. The methylene chloride extract was concentrated in vacuo and the residue was heated in an oil bath to 140° C. for 30 minutes. The mixture was cooled, partitioned between water and ethyl acetate. The ethyl acetate layer was separated, washed with 5% sodium hydroxide and then brine, dried over sodium sulfate, and evaporated. Purification by silica gel chromatography (40% ethyl acetate-hexane) gave 1-(4-amino-5-chloro-2-methoxyphenyl)-3-[1-(tert-butoxycarbonyl)piperidin-4-yl]-propan-1-one (1.5 g, 3.8 mmol), m.p. 133°-134° C.

Provenance & Evidence