Oxalic Acid → 4-Chloro-2-[[(1R)-1-phenyl-4-(1-pyrrolidinyl)butyl]oxy]-benzonitrile ethanedioate

HRID 352106Notes

Reaction equation

HRID 352106 reaction equation
[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:10][C@@H:11]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:12][CH2:13][CH2:14]I)[CH:3]=1.[NH:22]1[CH2:26][CH2:25][CH2:24][CH2:23]1.[C:27]([OH:32])(=[O:31])[C:28]([OH:30])=[O:29]>O1CCCC1.C(O)(C)C.CO>[C:27]([OH:32])(=[O:31])[C:28]([OH:30])=[O:29].[Cl:1][C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:10][C@@H:11]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[CH2:12][CH2:13][CH2:14][N:22]2[CH2:26][CH2:25][CH2:24][CH2:23]2)[CH:3]=1

Participants

7

Reactant 3

HCID 971Oxalic AcidHCID 31268PyrrolidineHCID 698282664-Chloro-2-[[(1r)-4-iodo-1-phenylbutyl]oxy]benzonitrile

Product 1

HCID 865883454-Chloro-2-[[(1R)-1-phenyl-4-(1-pyrrolidinyl)butyl]oxy]-benzonitrile ethanedioate

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 3776IsopropanolSolventHCID 8028TetrahydrofuranSolvent

Procedure

A solution of the product from Example 1 step (c) (200 mg) and pyrrolidine (0.15 ml) in tetrahydrofuran (5 ml) was stirred for 2 days. The solvent was removed in vacuo and the residue dissolved in water and aqueous potassium carbonate and extracted with ethyl acetate (three times). The combined organic extracts were washed with water, dried (Na2SO4) and evaporated to give an oil. To a solution of this amine in isopropanol (3 ml) was added a solution of oxalic acid (44 mg) in methanol (0.3 ml). The crystals that formed on cooling were collected and dried to afford the title compound as a white solid (163 mg). M.p. 157-158° C.

Workup

  1. customThe solvent was removed in vacuo
  2. dissolutionthe residue dissolved in water
  3. extractionaqueous potassium carbonate and extracted with ethyl acetate (three times)
  4. washThe combined organic extracts were washed with water
  5. dry with materialdried (Na2SO4)
  6. customevaporated
  7. customto give an oil
  8. customThe crystals that formed
  9. temperatureon cooling
  10. customwere collected
  11. customdried

Sources & evidence

ORD record
ord-22dcac02f6cb45b6988975761f1eac57
Source dataset
uspto-grants-2004_06
Patent number
US06743939B2

Reaction notes

Loading…