Sodium Hydroxide → 1-(1-((tert-butoxy)carbonyl)piperidin-4-yl)-1H-pyrazole-4-carboxylic acid

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Reaction Conditions

Reaction Steps

To a solution of 1H-pyrazole-4-carboxylic acid ethyl ester (701 mg, 5 mmol) in dry N,N-dimethylformamide (15 mL) at 0-5° C., under argon, was added 60% sodium hydride (480 mg, 1.2 eq). After stirring for 1 hour was added a solution of 4-methanesulfonyloxy-piperidine-1-carboxylic acid tert-butyl ester (1.53 g, 1.1 eq) in dry N,N-dimethylformamide (4 mL). The mixture was heated to 100° C., stirred for 6 hours then treated with water and extracted with ethyl acetate. The organic layer was separated (organic layer A). The aqueous layer was acidified with a 5% aqueous solution of potassium bisulfate and extracted with ethyl acetate giving, after separation, the organic layer B. The organic layer A was evaporated to dryness. The residue was treated with 20 mL of methanol, 5 mL of water and 1.12 g of sodium hydroxide (20 mmol) and stirred at room temperature for 2 days. The solvents were removed under reduced pressure, the residue treated with ethyl acetate and washed with 5% aqueous solution of potassium bisulfate giving the organic layer C. The combined organic layers B and C were dried over sodium sulfate and evaporated to dryness. The residue was triturated with diethyl ether and dried under vacuum affording 590 mg of title compound.

Provenance & Evidence