HCID 68699565, compound → HCID 68697251, compound

HRID 2244339Notes

Reaction equation

HRID 2244339 reaction equation
[C:1]([C:5]1[CH:23]=[CH:22][C:8]([CH2:9][NH:10][C:11](=O)[C:12]([F:20])([F:19])[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]>C1COCC1>[C:1]([C:5]1[CH:23]=[CH:22][C:8]([CH2:9][NH:10][CH2:11][C:12]([F:20])([F:19])[C:13]2[CH:14]=[CH:15][CH:16]=[CH:17][CH:18]=2)=[CH:7][CH:6]=1)([CH3:4])([CH3:2])[CH3:3]

Participants

3

Reactant 1

HCID 68699565HCID 68699565, compound

Product 1

HCID 68697251HCID 68697251, compoundYield 39%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

Borane-tetrahydrofuran complex solution (1 M in THF, 1.89 mL, 1.89 mmol) was added at 0° C. to a solution of N-(4-tert-butyl-benzyl)-2,2-difluoro-2-phenyl-acetamide (200 mg, 0.63 mmol) in THF (3.2 mL), then the ice bath was removed and the solution heated to reflux over 16 h. After cooling, the reaction was quenched by careful addition of 1 M aq. hydrochloric acid solution. The reaction mixture was neutralized with aq. sodium hydroxide solution and extracted with DCM. The organic layer was washed with brine, dried (MgSO4), evaporated, and chromatographed (SiO2, heptane-ethyl acetate gradient). The fractions containing the product were concentrated, the residue dissolved in 5% ethanolic sulfuric acid solution (2 mL). This solution was heated at reflux for 2 h, neutralized with 2 M aq. sodium hydroxide solution, and extracted with ethyl acetate. The organic layer was washed with brine, dried (MgSO4), and evaporated to produce the title compound (74 mg, 39%). Light yellow oil, MS (ISP) 304.3 (M+H)+.

Workup

  1. customthe ice bath was removed
  2. temperaturethe solution heated
  3. temperatureto reflux over 16 h
  4. temperatureAfter cooling
  5. customthe reaction was quenched by careful addition of 1 M aq. hydrochloric acid solution
  6. extractionextracted with DCM
  7. washThe organic layer was washed with brine
  8. dry with materialdried (MgSO4)
  9. customevaporated
  10. customchromatographed (SiO2, heptane-ethyl acetate gradient)
  11. additionThe fractions containing the product
  12. concentrationwere concentrated
  13. dissolutionthe residue dissolved in 5% ethanolic sulfuric acid solution (2 mL)
  14. temperatureThis solution was heated
  15. temperatureat reflux for 2 h
  16. extractionextracted with ethyl acetate
  17. washThe organic layer was washed with brine
  18. dry with materialdried (MgSO4)
  19. customevaporated

Sources & evidence

ORD record
ord-2a65914aa9ae4343be03e47c439b38df
Source dataset
uspto-grants-2010_03
Patent number
US07678818B2

Reaction notes

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