78385-84-9

The general procedure for the synthesis of 4-fluorodicyclo[2.2.2]octane-1-carboxylic acid from the compound (CAS: 78385-85-0) is as follows: Preparation of intermediate A51C: To a solution of intermediate A51B (80 mg, 0.430 mmol) in methanol (2 mL) was added slowly and dropwise 1 M sodium hydroxide solution (1 mL, 1.00 mmol). The reaction mixture was stirred overnight at room temperature and subsequently concentrated. The residue was acidified with 1 N hydrochloric acid to pH about 2 and subsequently extracted with ethyl acetate. The organic layers were combined, washed with saturated brine, dried over anhydrous sodium sulfate and filtered. Concentration of the filtrate gave the intermediate A51C (66 mg, 89% yield) as a white solid, which could be used in the next step of the reaction without further purification. 1H NMR (400 MHz, methanol-d4) δ ppm: 2.10-1.95 (m, 6H), 1.90-1.78 (m, 6H).

[1] Journal of Organic Chemistry, 1982, vol. 47, # 15, p. 2951 - 2957
[2] Patent: US9273058, 2016, B2. Location in patent: Page/Page column 529