Ethanol → HCID 58878078, compound

Temperature

72 °C

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).

1. temperatureto cool to room temperature
2. filtrationThe resulting precipitate was filtered off
3. washwashed with ethanol (2 L) and air
4. customdried
5. customto give
6. customa white solid (4381.6 g-contains solvent, dry weight estimated by 1H NMR at 2674.2 g), which
7. customwas split into four
8. additionTo each of the four portions was added
9. additiona mixture of ethanol and water (11.9 L EtOH, 4.9 L H2O)
10. custombefore isolating the solid
11. filtrationby filtration
12. washwashing with ethanol
13. customdrying the solid in a vacuum oven overnight at 40° C.

ORD record

ord-f14fdc7ec9e34200a1e30fb8510ad4fc

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09145354B2