Potassium Hydroxide → (S)-4-Fluoro-N-(1-(3-hydroxyazetidin-1-yl)-2,3-dimethylbutan-2-yl)-N,3-dimethylbenzamide

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Reaction Steps

HATU (0.408 g, 1.07 mmol) was added to a mixture of 4-fluoro-3-methylbenzoic acid (5.34 ml, 1.07 mmol) and DIPEA (2 mL, 11.45 mmol) in DMF (10 mL). After 10 min was (S)-1-(2,3-dimethyl-2-(methylamino)butyl)azetidin-3-ol (Compound Y) (0.1 g, 0.54 mmol) in DCM added. The resultant mixture was stirred at rt over night. The mixture was concentrated and the residue dissolved in DCM. The organic phase was washed with NaHCO3 (saturated) and brine. The filtrate was dried (Na2SO4) and concentrated under reduced pressure. MeOH (10 mL) and KOH (2.221 ml, 3.22 mmol) was added and the resultant mixture was stirred at rt for 3 days. The solvent was removed and the residue was purified by preparative HPLC to give the title compound (1.1 mg, 0.5%). Mixture of rotamers: 1H NMR (400 MHz, CDCl3) δ 0.91, 1.01, 2.29, 2.34-2.43, 2.81, 2.96, 3.03-3.56, 3.65-3.79, 3.79-3.96, 4.00-4.12, 4.28, 4.43-4.57, 6.92-7.06, 7.16-7.25. Total no of protons: 27. HRMS (M+H)+: calculated 323.2135. found 323.2113.

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