4-Methylmorpholine → 1,1-Dimethylethyl (3S)-3-[(3-chloro-4-cyanophenyl)amino]-4-hydroxybutanoate

Participants

Reaction Conditions

Reaction Steps

A solution of isobutyl chloroformate (2.01 g, 14.8 mmol) in THF (5 mL) was added dropwise to a solution of (2S)-2-[(3-chloro-4-cyanophenyl)amino]-4-[(1,1-dimethylethyl)oxy]-4-oxobutanoic acid (4.57 g, 14.1 mmol) and NMM (1.56 g, 15.5 mmol) in THF (50 mL) at −10° C. After stirring for 30 min, the reaction was filtered through a pad Celite and the filtrate was cooled to −10° C. To the cold filtrate, a solution of NaBH4 (0.80 g, 21 mmol) in H2O (10 mL) was added slowly and the reaction solution was stirred at −10° C. for 15 min and then at room temperature for 45 min. The reaction was quenched with aqueous NH4Cl and extracted with Et2O (2×). The organic extracts were washed with 5% Na2CO3, cold 0.1N HCl and H2O, dried over Na2SO4, filtered, and concentrated. The residue was purified via silica gel chromatography with 0% MeOH in CH2Cl2 grading to 3% MeOH in CH2Cl2 to afford the titled product (2.83 g, 64%) as a solid. 1H-NMR (CDCl3) δ: 1.45 (9H, s), 2.61 (2H, m), 3.79 (2H, d, J=4.4 Hz), 3.93 (1H, m), 6.55 (1H, dd, J=8 Hz, 4 Hz), 6.72 (1H, d, J=2 Hz), 7.41 (1H, d, J=8.8 Hz). LC-MS (ES) m/e 311.5 (M+H)+.

Provenance & Evidence