Reaction Steps
To a solution of triphosgene (254 mg, 0.87 mmol) in EtOAc (5 mL) at 0° C. was added solution of (1S,8aS)-1-o-tolylhexahydropyrrolo[1,2-a]pyrazin-6(7H)-one (400 mg, 1.73 mmol), DMAP (21 mg, 0.173 mmol) and TEA (524 mg, 5.19 mmol in EtOAc (5 mL). The mixture was stirred for 1.5 h, followed by addition of (R)-N-methyl-1-(3-methyl-5-(trifluoromethyl)phenyl)ethanamine (563 mg, 2.6 mmol) in EtOAc (2 mL) and TEA (524 mg, 5.19 mmol). The reaction was stirred at 50° C. for 48 h and quenched with water. The resulting mixture was extracted with EtOAc and the organic layer was washed with 1 M aqueous HCl solution, dried over anhydrous Na2SO4 and then concentrated in high vacuum. The residue was purified by silica gel chromatography (DCM/MeOH=20/1 to 10/1) to give the title compound (350 mg, yield: 85%). 1H NMR (400 MHz, CDCl3) δ ppm 7.32 (s, 1H), 7.25 (d, J=8.0 Hz, 1H), 7.19 (d, J=7.4 Hz, 2H), 7.14 (ddd, J=17.5, 10.0, 4.2 Hz, 2H), 7.00 (s, 1H), 5.48 (q, J=6.9 Hz, 1H), 4.22 (m, 2H), 3.71 (dd, J=17.0, 7.3 Hz, 1H), 3.29 (d, J=11.8 Hz, 1H), 3.11 (td, J=12.4, 2.7 Hz, 1H), 2.95 (td, J=11.9, 3.2 Hz, 1H), 2.64 (s, 3H), 2.54 (s, 3H), 2.48 (m, 2H), 2.34 (s, 3H), 1.87 (m, 1H), 1.67 (ddd, J=17.1, 13.1, 9.4 Hz, 1H), 1.37 (d, J=6.7 Hz, 3H); m/z (ES+): 474 [M+H]+.
