Sodium cyanoborohydride [MI] → HCID 67772039, compound

Participants

Reaction Steps

(S)-3,4-Difluoro-N-methyl-N-(3-methyl-1-oxobutan-2-yl)benzamide (Compound A2.3) (0.25 g, 0.98 mmol) in MeOH (1.5 mL) was added to 3-(methoxymethyl)azetidine hydrochloride (0.202 g, 1.47 mmol) and TEA (0.679 mL, 4.90 mmol) in MeOH (1.5 mL). Sodium cyanotrihydroborate (0.103 mL, 1.96 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 AD 5 μm 20×250 mm column and Heptan/EtOH/TEA 80/20/0.1, as mobile phase to give the title compound (69 mg, 21%). Enantiomeric excess: 99.9%. Mixture of rotamers: (400 MHz, CD3OD) δ 0.77-0.86, 0.93, 1.06, 1.70-1.90, 2.57-2.88, 2.94-3.09, 3.22-3.36, 3.40-3.57, 4.18-4.36, 7.23-7.52, 7.63-7.74. Total no of protons: 26. HRMS (M+H)+: calculated 341.2040. found 341.2051.

Provenance & Evidence