4-Toluenesulfonyl chloride → 1,1-Dimethylethyl (3S)-3-[(3-chloro-4-cyanophenyl)amino]-4-{[(4-methylphenyl)sulfonyl]oxy}butanoate

Participants

Reaction Conditions

Reaction Steps

p-Toluenesulfonyl chloride (18.2 g, 96 mmol) was added portion-wise to an ice cold solution of 1,1-dimethylethyl (3S)-3-[(3-chloro-4-cyanophenyl)amino]-4-hydroxybutanoate (27.0 g, 87 mmol) in pyridine (75 mL). After stirring at 0° C. for 15 min, ice bath was removed and the reaction was stirred at room temperature for 2.5 h. The reaction was poured into stirred, ice/H2O (400 mL). When the product solidified, it was filtered, and the solid washed well with H2O. The solid was dissolved in EtOAc (350 mL), and washed successively with H2O, aq. citric acid, and H2O. The EtOAc solution was treated with charcoal, dried (MgSO4), filtered, and the solvent evaporated. The crude product was triturated with a mixture of Et2O (150 mL) and petroleum ether (50 mL) to afford the pure product (35.0 g, 87%). 1H-NMR (CDCl3) δ: 1.42 (9H, s), 2.47 (3H, s), 2.60 (2H, m), 4.04 (1H, m), 4.22 (2H, m), 6.45 (1H, dd, J=8 Hz, 4 Hz), 6.56 (1H, d, J=2.4 Hz), 7.35 (3H, m), 7.75 (2H, d, J=8.4 Hz). LC-MS (ES) m/e 465.3 (M+H)+.

Provenance & Evidence