Potassium Carbonate → 3-[(2-Chloro-3-trifluoromethyl-benzyl)-diphenylethyl-amino]-propan-1-ol

Temperatur

85 °C

To a stirring solution of 3-bromo-propanol (5.9 mL, 65.4 mmol) in acetonitrile (500 ml) was added Nal (19.6 g, 131 mmol) and K2CO3 (18.1 g, 131 mmol). The mixture was stirred at 85° C. for 1 h, and then N-(2,2-diphenylethyl)-N-(2-chloro-3-trifluoromethyl-benzyl)amine (34.0 g, 87.2 mmol) was added. The reaction mixture was heated at 85° C. overnight. Solvent was removed, the residue was washed with H2O, and extracted twice with EtOAc. The EtOAc extracts were dried over Na2SO4, filtered, and concentrated. The crude mixture was purified by silica gel chromatography (35 g Redisep column, silica, 40 um, 60 Å, 35 mL/min, A: hexanes, B: EtOAc, B: 0% for 2 min, B: 0% to 10% over 10 min; B: 10% for 2 min; B: 10% to 20% over 15 min; B: 20% for 2 min; B: 20% to 30% over 40 min; detection at 214 nm) to give 13.3 g (29.7 mmol, 34%) of the title compound as a white solid. 1H NMR (CDCl3, 400 MHz) □: 7.6 (d, J=7.6 Hz, 1H), 7.3-7.1 (m, 12H), 4.2 (t, J=7.6 Hz, 1H), 3.8 (s, 2H), 3.6 (t, J=5.6 Hz, 2H), 3.2 (d, J=7.6 Hz, 2H), 2.8 (t, J=6.0 Hz, 2H), 2.5 (s, 1H), 1.7 (m, 2H);

1. temperatureThe reaction mixture was heated at 85° C. overnight
2. customSolvent was removed
3. washthe residue was washed with H2O
4. extractionextracted twice with EtOAc
5. dry with materialThe EtOAc extracts were dried over Na2SO4
6. filtrationfiltered
7. concentrationconcentrated
8. customThe crude mixture was purified by silica gel chromatography (35 g Redisep column, silica, 40 um, 60 Å, 35 mL/min
9. waitA: hexanes, B: EtOAc, B: 0% for 2 min
10. waitB: 0% to 10% over 10 min
11. waitB: 10% for 2 min
12. waitB: 10% to 20% over 15 min
13. waitB: 20% for 2 min
14. waitB: 20% to 30% over 40 min

ORD-Eintrag

ord-1125acb2572e49fa8cef1f59e157f4da

Quelldatensatz

uspto-grants-2008_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07365085B2