4-Chlorobenzoic Acid → HCID 57345448, compound

Participants

Reaction Steps

(S)-1-(3-Methyl-2-(methylamino)butyl)azetidin-3-ol (Compound K2) (1.0 g, 3.48 mmol) was dissolved in DCM (13.3 mL), DIPEA (1.82 mL, 10.4 mmol), 4-chlorobenzoic acid (0.654 g, 4.18 mmol), and TBTU (1.45 g, 4.53 mmol) were added. The reaction was stirred for 2 h at rt whereupon saturated NaHCO3 (aq.) was added. The organic layer was separated and evaporated in vacuo. The residue was redissolved in THF/water and 3.8 M NaOH was added (1.2 mL) the reaction mixture was stirred for 15 min whereupon water was added and some of the organics was evaporated. The water phase was extracted with DCM, separated using a phase-separator and evaporated. The residue was evaporated and redissolved in DMSO and purified by preparative HPLC on a XBridge C18 column (10 μm 250×50 ID mm) using a gradient of 15-55% Acetonitrile in H2O/ACN/NH3 95/5/0.2 buffer over 30 minutes with a flow of 100 mL/min. The compounds were detected by UV at 220 nm to give the target compound pooling of pure fractions and evaporation of solvents in vacuo gave (S)-4-chloro-N-(1-(3-hydroxyazetidin-1-yl)-3-methylbutan-2-yl)-N-methylbenzamide (0.67 g, 62%). Mixture of rotamers: 1H NMR (600 MHz, CD3OD) δ 0.81-0.88, 0.99, 1.09, 1.72-2.00, 1.95, 2.63-2.76, 2.80, 2.85-2.97, 3.12-3.19, 3.26-3.35, 3.46-3.67, 4.10-4.19, 4.28-4.56, 7.44-7.54. Ratio major:minor:1:0.2. Total no of protons: 27.3 (5.3 from CH3CO2H). HRMS (M+H)+: calculated 311.1526. found 311.1528.

Provenance & Evidence