acetyl (2S)-2-hydroxy-2-phenylacetate → HCID 131733522, compound

Participants

Reaction Steps

Step 11—To a stirred solution of 3-{[(1R)-1-[3-(6-aminopyridine-3-carbonyl)-4-chloro-2-fluorophenyl]propyl]-amino}butanamide (237 g, 603 mmol) in EtOH (1900 mL) at 78° C. was added (+)-O-acetyl-L-mandelic acid (117 g, 603 mmol). The mixture was kept at 78° C. for 10 minutes then allowed to cool to room temperature (with stirring) providing a precipitate. After stirring overnight the solid was collected by filtration, washed with EtOH (1.25 Vol), then Et2O (1.7 Vol) and dried at 40° C. under vacuum providing (3S)-3-{[(1R)-1-[3-(6-aminopyridine-3-carbonyl)-4-chloro-2-fluorophenyl]propyl]-amino}butanamide (+)-O-acetyl-L-mandelic acid salt (206 g) diastereomer ratio of 97.5:2.5 in favour of the desired diastereomer. 1H NMR (400 MHz, DMSO-d6): 8.15 (1H, d), 7.78 (1H, dd), 7.64 (1H, t), 7.52-7.37 (6H, m), 7.31 (3H, d), 6.79 (1H, s), 6.54 (1H, d), 5.83-5.73 (1H, m), 4.01 (1H, t), 2.87-2.69 (1H, m), 2.62-2.52 (1H, m), 2.22-2.01 (2H, m), 2.12 (3H, s), 1.81-1.66 (1H, m), 1.66-1.50 (1H, m), 0.95 (3H, d), 0.78 (3H, t).

Provenance & Evidence