Lithium Hydroxide → HCID 68284762, compound

Participants

Reaction Conditions

Reaction Steps

To a 100 mL round bottom flask was added methyl 5-bromopyridine-2-carboxylate (0.5 g, 2.3 mmol) followed by DMF (5 mL) and sodium sulfanide (259 mg, 4.6 mmol). The reaction was heated at 65° C. overnight. Bromomethylcyclobutane (260 μL, 2.3 mmol) was added and the reaction was allowed to stir for 30 minutes while cooling to 25° C. The reaction was then quenched with brine and extracted with ethyl acetate 3 times. The organic layers were combined and dried over sodium sulfate and the solvent was evaporated. The crude reaction mixture was then treated with 50 mL of Clorox® bleach and allowed to stir for 30 minutes. LiOH (5 mL of 3M) was added and the reaction was allowed to stir for 1 h. The reaction was extracted with ethyl acetate and the organic layer was discarded. The aqueous layer was acidified to pH 2 and extracted with ethyl acetate 3 times. The organic layers were combined and dried over sodium sulfate. The crude product was purified via HPLC (1-99%) ACN:H2O with a 0.1% TFA modifier. 5-(Cyclobutylmethylsulfonyl)picolinic acid (39 mg) was isolated as a white solid. 1H NMR (400 MHz, MeOD) δ 9.11 (dd, J=2.2, 0.8 Hz, 1H), 8.47 (dd, J=8.2, 2.2 Hz, 1H), 8.35 (dd, J=8.2, 0.8 Hz, 1H), 3.47 (d, J=7.3 Hz, 2H), 2.80-2.66 (m, 1H), 2.11-2.00 (m, 2H), 1.97-1.75 (m, 4H).

Provenance & Evidence