Triethylamine → (R)-3,5-difluoro-N-(4-(1-(1-methylethylsulfonamido)propan-2-yl)phenyl)benzamide

Temperature

20 °C

To a 0° C. solution of [(2R)-2-(4-aminophenyl)propyl][(methylethyl)sulfonyl]amine (21.5 g, 0.0838 mol) and triethylamine (9.75 g, 13.4 mL, 0.0964 mol) in CH2Cl2 (86 mL) was added 3,5-difluorobenzoyl chloride (16.3 g, 0.0922 mol) dropwise over 30 min. After the addition was complete, the reaction mixture was stirred at 20° C. for 1 hour. The reaction mixture was washed with deionized water (2×100 mL) and 0.1 N HCl (2×100 mL). The organic phase was diluted with acetone (50 mL) to ensure complete dissolution of the product and the organic phase was washed with saturated K2CO3 (100 mL), 0.1 N HCl (100 mL), dried (MgSO4, 3 g), filtered and co-evaporated with EtOAc to afford an oil. This oil was diluted with diethyl ether (125 mL), which induced crystallization. The solids were collected by filtration, washed with diethyl ether (2×20 mL), and dried under reduced pressure at room temperature overnight to afford N-[4-((1R)-1-methyl-2-{[(methylethyl)sulfonyl]amino}ethyl)phenyl](3,5-difluorophenyl)carboxamide (31.8 g, 95.7%) as a white crystalline powder.

1. additionAfter the addition
2. washThe reaction mixture was washed with deionized water (2×100 mL) and 0.1 N HCl (2×100 mL)
3. additionThe organic phase was diluted with acetone (50 mL)
4. dissolutiondissolution of the product
5. washthe organic phase was washed with saturated K2CO3 (100 mL), 0.1 N HCl (100 mL)
6. dry with materialdried (MgSO4, 3 g)
7. filtrationfiltered
8. customto afford an oil
9. customcrystallization
10. filtrationThe solids were collected by filtration
11. washwashed with diethyl ether (2×20 mL)
12. customdried under reduced pressure at room temperature overnight

ORD record

ord-de2648701007423a9a229f5721e6968b

Source dataset

uspto-grants-2004_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06803484B2