4-Methylmorpholine → Tert-butyl 4-(2-methyl-4-(methylcarbamoyl)phenyl)piperazine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

To a suspension of 4-(4-(tert-butoxycarbonyl)piperazin-1-yl)-3-methylbenzoic acid (2.0 g, 6.24 mmol), methanamine hydrochloride (0.506 g, 7.49 mmol), N1-((ethylimino)methylene)-N3,N3-dimethylpropane-1,3-diamine hydrochloride (1.795 g, 9.36 mmol), and 1H-benzo[d][1,2,3]triazol-1-ol hydrate (1.434 g, 9.36 mmol) in DMF (Volume: 8.5 mL) was added 4-methylmorpholine (3.43 mL, 31.2 mmol) at 23° C. The reaction was stirred at 23° C. for 2 hr. The reaction mixture was diluted with water (100 mL) and the product was extracted with EtOAc (3×100 mL). The organic extracts were combined, washed with 1N HCl (50 mL), saturated NaHCO3 (50 mL), H2O (50 mL), brine (50 mL) dried over MgSO4, filtered, rinsed with EtOAc, and dried in vacuo to provide tert-butyl 4-(2-methyl-4-(methylcarbamoyl)phenyl)piperazine-1-carboxylate (1.90 g, 5.70 mmol, 91% yield) as a yellow oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.42 (s, 9 H) 2.28 (s, 3 H) 2.75 (d, J=4.55 Hz, 3 H) 2.79-2.87 (m, 4 H) 3.42-3.52 (m, 4 H) 7.03 (d, J=8.34 Hz, 1 H) 7.62 (dd, J=8.34, 2.27 Hz, 1 H) 7.64-7.69 (m, 1 H) 8.26 (q, J=4.46 Hz, 1 H). ESI-MS: m/z 334.3 (M+H)+.

Provenance & Evidence