Methyl p-toluenesulfonate → 3-(2,2-Dimethylpropyl)-1-cyclobutene-1-carboxylic acid

Participants

Reaction Conditions

Reaction Steps

Ethyl 3-(2,2-dimethylpropyl)-2-piperidin-1-ylcyclobutanecarboxylate (1470 g) and methyl p-toluenesulfonate (417 mL) were mixed. After the mixture was stirred at 105° C. for 2 hr, water (2100 mL) was poured into the reaction mixture and the aqueous layer was extracted. The aqueous layer was washed with tert-butyl methyl ether/hexane=1/1 (800 mL) and hexane (600 mL). To the aqueous layer was added potassium hydroxide (663 g) at ice temperature and the mixture was stirred at 100° C. for 2 hr. After the reaction mixture was washed with tert-butyl methyl ether/hexane=1/1 (600 mL×2), concentrated hydrochloric acid (500 mL) and 6 N hydrochloric acid (606 mL) were added to the aqueous layer at ice temperature. The mixture was extracted with ethyl acetate (600 mL×2). The combined organic layer was washed with water (1 L×2) and brine (500 mL), then dried over magnesium sulfate. The magnesium sulfate was filtered off and the filtrate was concentrated in vacuo to give the title compound (278 g) as a crude product.

Provenance & Evidence