Sodium Chloride → HCID 54197900, compound

Participants

Reaction Conditions

Reaction Steps

4-Bromopyridine hydrochloride (10.05 g, 51.8 mmol) was treated with potassium carbonate (7.15 g, 51.8 mmol) in water (50 mL), and the resulting solution was saturated with sodium chloride. The 4-bromopyridine free base was extracted with diethyl ether, and the solution was stored under N2 over 3 angstrom molecular sieves for 1 h. The 4-bromopyridine solution was slowly transferred by cannula to a stirred solution of 2.5 M butyllithium in hexane (21.2 mL, 53 mmol) in anhydrous diethyl ether (100 mL), maintained at −78° C. under N2. The reaction mixture was stirred for 30 min., and then a solution of cis-1,2-cyclohexanedicarboxylic anhydride (8.33 g, 54 mmol) in anhydrous tetrahydrofuran (150 mL) was added by cannula. The reaction mixture was stirred at −78° C. for 1 h and then allowed to warm to 20° C. The reaction mixture was quenched by addition of water (200 mL), and the aqueous layer was separated and acidified to pH=4 by addition of 6 M hydrochloric acid. The aqueous layer was saturated with sodium chloride and extracted with a (1:1) mixture of ethyl acetate and tetrahydrofuran (400 mL). The organic layer was washed with sat. NaCl, dried over MgSO4, filtered, and evaporated to give cis-2-(4-pyridylcarbonyl)cyclohexanecarboxylic acid, as a solid, which was used immediately in the next step.

Provenance & Evidence