Hydrochloric Acid → 6-Chloro-5-(1-fluorocyclobutyl)pyridine-2-carboxylic acid

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Reaction Conditions

Reaction Steps

Aqueous phosphate buffer (pH=6.7, 0.7 mL) and TEMPO (2.54 mg, 16.2 μmol) were added to a solution of (6-chloro-5-(1-fluorocyclobutyl)pyridin-2-yl)methanol (Example 130 d, 50 mg, 232 μmol) in acetonitrile (1 mL) under an argon atmosphere. The reaction mixture was warmed to 35° C. A solution of sodium chlorite (52.4 mg, 464 μmol) in 150 μL water and a solution of sodium hypochlorite (2.66 mg, 2.19 μL, 4.64 μmol) in 100 μL water were added simultaneously over a period of 30 min. Stirring was continued at 35° C. for 20 h. Water (40 mL) and 2 N NaOH solution (8 mL) were added. The mixture was poured into an ice cold Na2SO3 solution (1.62 Na2SO3 g in 30 mL water) and stirred for 30 min. at ambient temperature. Under ice cooling the mixture was acidified with 25 mL 2 N HCl solution and extracted with a mixture of 100 mL EtOAc and 20 mL THF. The organic layer was dried over Na2SO4, filtered and the solvent concentrated in vacuo to give the title compound (66 mg, 90%) as yellow oil, MS(ESI): m/e=230.4 [MH+].

Provenance & Evidence