反应详情

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.

1. temperatureis heated
2. temperatureat reflux under N2 for 2 hours
3. customthe residue is partitioned between 50 mL of H2O and 100 mL of 10% NaOH and 3×100 mL of CH2Cl2
4. washwashed with 2×50 mL of H2O
5. dry with materialdried with Na2SO4
6. customevaporated in vacuo
7. customto afford 9.44 g of partly crystallized dark orange material
8. extractionextracted with 50 mL of 10% aqueous HCl, 50 mL of H2O, 50 mL of 10% HCl and 50 mL of H2O
9. extractionextracted with 3×100 mL of CH2Cl2
10. washThe CH2Cl2 extracts are washed with 2×50 mL of H2O
11. dry with materialdried with Na2SO4
12. customto give an off-white solid
13. customRecrystallization from hexane