8-Phenyloctan-1-amine → N-(8-Phenyl-octyl)-3,5-bis-(m-chlorophenyl)4-(2-hydroxyethoxy)-benzamide

Temperature

0 °C

To a flamed dried round bottom flask with 8-phenyloctyl amine (0.484 mL, 2.43 mmol) and THF (5 mL) cooled to 0° C. was added n-BuLi (0.972 mL, 2.5 M in hexane, 2.43 mmol) dropwise over a 5 min. period. The resulting solution was allowed to stir 5 min. and then warmed to room temperature for 30 min. This solution was then added dropwise to a solution of 3,5-bis-(m-chlorophenyl)-4-(2-hydroxyethoxy)benzoic acid ethyl ester (0.300 g, 0.696 mmol) in THF (15 mL) at −20° C. This final mixture was stirred at −20° C. for 15 min and then warmed to room temperature for 15 min. At this point, the reaction mixture was quenched with H2O (10 mL) and diluted with EtOAc (200 mL). The organic layer was washed with 1 N HCl (20 mL), sat. aq. NaHCO3 (20 mL), and brine (20 mL) and then dried (MgSO4). After concentration, the residue was purified by the Biotage Flash 40 (20 to 40% EtOAc/petroleum ether gradient) to afford the product (0.267 g, 65%) as a clear oil; 1H NMR (400 MHz, CDCl3) δ 1.09-1.48 (m, 9H), 1.48-1.72 (m, 4H), 2.58 (t, J=6.8 Hz, 2H), 3.30-3.35 (m, 2H), 3.35-3.41 (m, 2H), 3.46 (dd, J=6.8, 13.0 Hz, 2H), 6.07-6.18 (m, 1H), 7.11-7.19 (m, 3H), 7.21-7.31 (m, 2H), 7.35-7.44 (m, 4H), 7.44-7.57 (m, 2H), 7.63 (s, 2H), 7.77 (s, 2H); mass spectrum [(+) ESI], m/z 590 (M)+.

1. temperaturewarmed to room temperature for 30 min
2. temperaturewarmed to room temperature for 15 min
3. customAt this point, the reaction mixture was quenched with H2O (10 mL)
4. additiondiluted with EtOAc (200 mL)
5. washThe organic layer was washed with 1 N HCl (20 mL), sat. aq. NaHCO3 (20 mL), and brine (20 mL)
6. dry with materialdried (MgSO4)
7. concentrationAfter concentration
8. customthe residue was purified by the Biotage Flash 40 (20 to 40% EtOAc/petroleum ether gradient)

ORD record

ord-6b71a0aad4704d5aac0c30a7a795c525

Source dataset

uspto-grants-2004_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06765021B2