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

HRID 1607187Notes

Reaction equation

HRID 1607187 reaction equation
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]

Participants

5

Reactant 3

HCID 702EthanolHCID 6385Tert-ButylamineHCID 146210263-(2-Bromo-1-hydroxyethyl)-2,5-difluorobenzonitrile

Product 1

HCID 146210273-[2-(Tert-butylamino)-1-hydroxyethyl]-2,5-difluorobenzonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-5648eddcf6c34bfe938c7e8c76dbfecd
Source dataset
uspto-grants-1989_09
Patent number
US04863959

Reaction notes

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