Water → 2-[[(1S)-2-Amino-1-phenylethyl]oxy]-4-chloro-5-fluorobenzonitrile (E)-butenedioate

HRID 1354392Notes

Reaction equation

HRID 1354392 reaction equation
[N:1]([CH2:4][C@@H:5]([O:12][C:13]1[CH:20]=[C:19]([Cl:21])[C:18]([F:22])=[CH:17][C:14]=1[C:15]#[N:16])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1)=[N+]=[N-].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O.[C:43]([OH:50])(=[O:49])/[CH:44]=[CH:45]/[C:46]([OH:48])=[O:47]>C1COCC1.C(O)C>[C:43]([OH:50])(=[O:49])/[CH:44]=[CH:45]/[C:46]([OH:48])=[O:47].[NH2:1][CH2:4][C@@H:5]([O:12][C:13]1[CH:20]=[C:19]([Cl:21])[C:18]([F:22])=[CH:17][C:14]=1[C:15]#[N:16])[C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][CH:7]=1

Participants

7

Reactant 4

HCID 962Water2×HCID 11776TriphenylphosphineHCID 444972Fumaric AcidHCID 865989742-[[(1S)-2-Azido-1-phenylethyl]oxy]-4-chloro-5-fluorobenzonitrile

Product 1

HCID 1317264602-[[(1S)-2-Amino-1-phenylethyl]oxy]-4-chloro-5-fluorobenzonitrile (E)-butenedioate

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
60 °C

Procedure

The product from step (b) (2.79 g) in dry THF (80 ml) was treated with triphenylphosphine (3.47 g) and water (12 ml) and the mixture heated at 60° C. for 2 h. The reaction mixture was cooled, poured into water, and extracted with ethyl acetate which was washed with water and dried (MgSO4). The solvent was evaporated and the residue purified by chromatography (silica, ethyl acetate and then 10% 7M ammonia in methanol/dichloromethane as eluent) to give an oil. This was dissolved in ethanol (10 ml), treated with fumaric acid (70.3 mg) and heated until a clear solution was obtained. The mixture was evaporated and the residue triturated with ether to give after filtration and drying in vacuo the final compound (222 mg).

Workup

  1. temperatureThe reaction mixture was cooled
  2. extractionextracted with ethyl acetate which
  3. washwas washed with water
  4. dry with materialdried (MgSO4)
  5. customThe solvent was evaporated
  6. customthe residue purified by chromatography (silica, ethyl acetate
  7. custom10% 7M ammonia in methanol/dichloromethane as eluent) to give an oil
  8. temperatureheated until a clear solution
  9. customwas obtained
  10. customThe mixture was evaporated
  11. customthe residue triturated with ether
  12. customto give
  13. filtrationafter filtration
  14. dry with materialdrying in vacuo the final compound (222 mg)

Sources & evidence

ORD record
ord-b319908457fb432397bcdd58aba72b35
Source dataset
uspto-grants-2007_05
Patent number
US07223794B2

Reaction notes

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