Acetic Acid → HCID 67774026, compound

Participants

Reaction Steps

(S)-4-Chloro-N-methyl-N-(3-methyl-1-oxobutan-2-yl)benzamide (Compound A2.2) (0.12 g, 0.47 mmol) dissolved in DCM was added to piperidin-4-ol (72 mg, 0.71 mmol) and acetic acid (0.135 mL, 2.36 mmol) in MeOH (2 mL). Sodium cyanotrihydroborate (0.059 g, 0.95 mmol) was added and the resultant mixture was stirred at rt over night. The solvent was removed and the residue diluted with DCM. The organic phase was washed with LiOH (aq., 3 mL, 1M), filtered through a phase separator and concentrated under reduced pressure. The residue was purified by preparative HPLC. The product containing fractions was concentrated and the residue was purified a second time by preparative HPLC using Chiralpak IC 5 μm 20×250 mm column and Heptan/EtOH/TEA 60/40/0.1, as mobile phase to give the title compound (4 mg, 2.5%). Enantiomeric excess: 99.8%. Mixture of rotamers: (600 MHz, CD3OD) δ 0.87, 0.92, 0.96, 1.03, 1.42-1.62, 1.71-1.90, 1.92-2.03, 2.14-2.21, 2.26-2.38, 2.42-2.50, 2.55-2.79, 2.88-2.93, 3.01, 3.28-3.38, 3.52-3.64, 4.43-4.56, 7.37-7.41, 7.43-7.52.

Provenance & Evidence