Ethanol → HCID 58878078, compound

Participants

Reaction Conditions

Reaction Steps

Step 4—Three runs were carried out in parallel and combined in the work-up. A mixture of 1-(4-chloro-2-fluoro-phenyl)-propylamine (497.6 g, 2.65 mol, 1.0 eq) from Step 3, ethanol and water (3.1 L ethanol/1.3 L water) and L-aspartic acid (353 g, 2.65 mol, 1.0 eq) was heated to 72° C. (oil bath) for 1 hour and then allowed to cool to room temperature. The resulting precipitate was filtered off, washed with ethanol (2 L) and air dried to give a white solid (4381.6 g-contains solvent, dry weight estimated by 1H NMR at 2674.2 g), which was split into four. To each of the four portions was added a mixture of ethanol and water (11.9 L EtOH, 4.9 L H2O) and the resulting mixture was then stirred at room temperature overnight before isolating the solid by filtration, washing with ethanol, and drying the solid in a vacuum oven overnight at 40° C., to give (R)-1-(4-chloro-2-fluoro-phenyl)-propylamine as the aspartate salt, a white solid (1409.2 g). 1H NMR (400 MHz, DMSO-d6): 7.56 (1H, t), 7.34 (1H, dd), 7.29 (1H, dd), 4.03 (1H, t), 3.68 (1H, dd), 2.67 (1H, dd), 2.38 (1H, dd), 1.69-1.49 (2H, m), 0.80 (3H, t).

Provenance & Evidence