Methyl p-toluenesulfonate → 3-Isobutyl-1-cyclobutenecarboxylic acid

Participants

Reaction Conditions

Reaction Steps

Ethyl 3-isobutyl-2-piperidin-1-ylcyclobutanecarboxylate (994 g) and methyl p-toluenesulfonate (337 mL) were mixed. The mixture was stirred at 110° C. for 2 hr and water (1100 mL) was added to the mixture. The resulting mixture was washed with tert-butyl methyl ether/hexane=1/1 (600 mL) and hexane (600 mL). To the aqueous layer was added potassium hydroxide (503 g) at ice temperature. The resulting mixture was stirred at 95° C. for 4 hr. The reaction mixture was washed with diethyl ether (500 mL) and diethyl ether/hexane=1/1 (500 mL). To the aqueous layer was added concentrated hydrochloric acid (672 mL) at ice temperature. The mixture was extracted with ethyl acetate (1 L×2). The combined organic layer was washed with water (500 mL×2) and brine (500 mL), then dried over sodium sulfate. The sodium sulfate was filtered off and the filtrate was concentrated in vacuo to give the title compound (240 g) as a crude product.

Provenance & Evidence