Hydrochloric Acid → HCID 58979664, compound

Participants

Reaction Steps

To a solution of 760 mg (2.1 mmol) of methyl(2S)-2-[({[1-(4-fluorobenzyl)cyclobutyl]methoxy}carbonyl)amino]hexanoate in 5 mL of tetrahydrofuran was added a solution of 105 mg (2.5 mmol) of lithium hydroxide monohydrate in 5 mL of water. The reaction was heated briefly to promote homogeneity and then let stir at room temperature for 18 h. The reaction was diluted with water, acidified with iced 1M hydrochloric acid, extracted with ethyl acetate, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting carboxylic acid was dissolved in 50 mL of dichloromethane before 630 mg (2.1 mmol) of (triphenylphosphoranylidene) acetonitrile was added. The mixture was cooled to 0° C. before a catalytic amount of N,N-dimethylaminopyridine was added followed by 400 mg (2.1 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride. The reaction was allowed to warm to room temperature and stirred for 18 h. The mixture was concentrated under reduced pressure and the residue was purified by silica gel chromatography eluting with 1:9 ethyl acetate:dichloromethane to afford 400 mg (300%) of [1-(4-fluorobenzyl)cyclobutyl]methyl(1S)-1-[cyano(triphenylphosphoranylidene)acetyl]pentylcarbamate. 1H NMR (300 MHz, DMSO-d6) δ 7.75 (m, 3H), 7.50-7.68 (m, 12H), 7.22 (m, 3H), 7.01 (t, J=9 Hz, 2H), 4.56 (m, 1H), 3.81 (dd, J=11 Hz, J=39 Hz, 2H), 2.77 (s, 2H), 1.70-1.95 (m, 7H), 1.61 (m, 1H), 1.38 (m, 4H), 0.92 (t, J=7 Hz, 3H). ES-LCMS m/z 635 (M+H).

Provenance & Evidence