Bromoacetonitrile → HCID 86663245, compound

HRID 337063Notes

Reaction equation

HRID 337063 reaction equation
[NH2:1][C:2]1[CH:3]=[C:4]([CH:10]=[C:11]([F:14])[C:12]=1[CH3:13])[C:5]([O:7][CH2:8][CH3:9])=[O:6].[CH2:15]([N:17](C(C)C)C(C)C)[CH3:16].BrCC#N>C1COCC1>[C:15]([CH2:16][NH:1][C:2]1[CH:3]=[C:4]([CH:10]=[C:11]([F:14])[C:12]=1[CH3:13])[C:5]([O:7][CH2:8][CH3:9])=[O:6])#[N:17]

Participants

5

Reactant 3

HCID 11534Bromoacetonitrile3×HCID 81531DiisopropylethylamineHCID 52982956Ethyl 3-amino-5-fluoro-4-methylbenzoate

Product 1

HCID 86663245HCID 86663245, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 3-amino-5-fluoro-4-methyl-benzoic acid, ethyl ester (Example 169b, 1.2 g) in THF (10 mL) at room temperature was added N-ethyldiisopropylamine (1.28 mL) followed by bromoacetonitrile (0.51 mL) and the reaction was heated at reflux for 14 h. Additional bromoacetonitrile (0.21 mL) was added and the mixture was heated at reflux for 6 h. Further bromoacetonitrile (0.21 mL) was added and heating was continued for a further 12 h. After cooling to room temperature the reaction was concentrated. Aqueous HCl (30 mL, 1N) and ethyl acetate (30 mL) were added. The layers were separated and the organic fraction was dried (Na2SO4), filtered and concentrated to give the subtitle product (1.43 g) as a solid.

Workup

  1. temperaturethe reaction was heated
  2. temperatureat reflux for 14 h
  3. temperaturethe mixture was heated
  4. temperatureat reflux for 6 h
  5. temperatureheating
  6. concentrationwas concentrated
  7. additionAqueous HCl (30 mL, 1N) and ethyl acetate (30 mL) were added
  8. customThe layers were separated
  9. dry with materialthe organic fraction was dried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated

Sources & evidence

ORD record
ord-426773d646704d6fa17d97ba2b73553e
Source dataset
uspto-grants-2014_11
Patent number
US08889692B2

Reaction notes

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