Ethanol → 3-[2-(Tert-butylamino)-1-hydroxyethyl]-2,5-difluorobenzonitrile

Reaktionsgleichung

Br[CH2:2][CH:3]([C:5]1[C:6]([F:14])=[C:7]([CH:10]=[C:11]([F:13])[CH:12]=1)[C:8]#[N:9])[OH:4].[C:15]([NH2:19])([CH3:18])([CH3:17])[CH3:16].CCO>C(Cl)Cl>[C:15]([NH:19][CH2:2][CH:3]([C:5]1[C:6]([F:14])=[C:7]([CH:10]=[C:11]([F:13])[CH:12]=1)[C:8]#[N:9])[OH:4])([CH3:18])([CH3:17])[CH3:16]

Komponenten

Versuchsvorschrift

A stirred mixture of 10.2 g of 3-(2-bromo-1-hydroxyethyl)-2,5-difluorobenzonitrile, 100 mL of t-butylamine and 100 mL of EtOH is heated at reflux under N2 for 2 hours. The mixture is stripped in vacuo and the residue is partitioned between 50 mL of H2O and 100 mL of 10% NaOH and 3×100 mL of CH2Cl2. The CH2Cl2 layers are combined, washed with 2×50 mL of H2O, dried with Na2SO4 and evaporated in vacuo to afford 9.44 g of partly crystallized dark orange material. This material is dissolved in 100 mL of CH2Cl2 and extracted with 50 mL of 10% aqueous HCl, 50 mL of H2O, 50 mL of 10% HCl and 50 mL of H2O. The combined aqueous acidic extracts are basified with 10% aqueous NaOH in ice and extracted with 3×100 mL of CH2Cl2. The CH2Cl2 extracts are washed with 2×50 mL of H2O, dried with Na2SO4 and stripped in vacuo to give an off-white solid. Recrystallization from hexane gives 5.8 g of 3-[2-(tert-butylamino)-1-hydroxyethyl]-2,5-difluorobenzonitrile, m.p. 99°-101° C. The mass spectrum shows an M+1 ion at 255. Infrared and NMR spectral data are consistent.