Reacción #78759

Ecuación de reacción

(3-phenoxyphenyl)[[(2′-(trifluoromethyl)[1,1′-biphenyl]-3-yl]methyl]amino]-1,1,1-tri-fluoro-2-propanol

K2CO3

3-[(3-phenoxyphenyl)[[3-bromophenyl] methyl]-amino]-1,1,1-trifluoro-2-propanol

2-(tri-fluoromethyl)phenylboronic acid

→

3-[(3-phenoxyphenyl)[[2′-(trifluoromethyl)[1,1′-biphenyl]-3-yl]methyl]amino]-1,1,1-trifluoro-2-propanol

Disolventes

EtOH

water

DMF

toluene

EtOH

Condiciones de reacción

Tratamiento posterior

1. 1
   TemperaturaThe slurry was heated
2. 2
   Temperaturato reflux under argon for 18 h
3. 3
   Extracciónextracted with ethyl acetate
4. 4
   LavadoThe organic layer was washed with brine
5. 5
   Secadodried (MgSO4)
6. 6
   Otroevaporated to an oil
7. 7
   OtroPurification by flash chromatography on silica gel eluting with 20% ethyl acetate in hexane
8. 8
   Otrogave an oil which
9. 9
   Otrodried in vacuo
10. 10
    Otroto give 0.32 g (55%) of the

Procedimiento

To a toluene (8 mL) solution of 3-[(3-phenoxyphenyl)[[3-bromophenyl] methyl]-amino]-1,1,1-trifluoro-2-propanol (0.51 g, 1.1 mmol) from EX-595B was added 2-(tri-fluoromethyl)phenylboronic acid (0.33 g, 1.7 mmol) and DMF (3 mL). To the resulting solution was added K2CO3 (0.31 g, 2.2 mmol) and Pd(PPh3)4 (0.060 g, 0.05 mmol). The slurry was heated to reflux under argon for 18 h. The cooled mixture was poured into water and extracted with ethyl acetate. The organic layer was washed with brine, dried (MgSO4) and evaporated to an oil. Purification by flash chromatography on silica gel eluting with 20% ethyl acetate in hexane gave an oil which was dissolved in EtOH, stripped and dried in vacuo to give 0.32 g (55%) of the desired 3-[(3-phenoxyphenyl)[[(2′-(trifluoromethyl)[1,1′-biphenyl]-3-yl]methyl]amino]-1,1,1-tri-fluoro-2-propanol product as a colorless oil. Anal. calcd. for C29H23NO2F6.0.8 EtOH: C, 64.67; H, 4.93; N, 2.46. Found: C, 64.53; H, 4.69; N, 2.49. HRMS calcd. 532.1711 [M+H]+, found: 532.1708. 1H NMR (C6D6) δ 1.72 (d, 1H), 3.17 (dd, 1H), 3.46 (dd, 1H), 3.72 (m, 1H), 4.23 (s 2H), 6.33 (dd, 1H), 6.43 (dd, 1H), 6.52 (t, 1H), 6.82 (m, 2H), 6.9-7.1 (m, 11H), 7.43 (d, 1H).

Fuente