Dimethylformamide → HCID 59331615, compound

HRID 1881816Notes

Reaction equation

HRID 1881816 reaction equation
[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[CH:13][CH:12]=2)[C:8]([OH:10])=O)[CH2:5][CH2:4][CH2:3][CH2:2]1.[C:21](Cl)(=[O:25])[C:22](Cl)=O.[CH3:27]N(C)C=O>ClCCl.C(OCC)(=O)C.Cl>[CH:1]1([CH2:6][CH:7]([C:11]2[CH:16]=[CH:15][C:14]([S:17]([CH3:20])(=[O:19])=[O:18])=[CH:13][CH:12]=2)[C:8](=[O:10])[CH2:27][C:21](=[O:25])[CH3:22])[CH2:2][CH2:3][CH2:4][CH2:5]1

Participants

7

Reactant 3

HCID 6228DimethylformamideHCID 65578Oxalyl chlorideHCID 120694893-Cyclopentyl-2-(4-methanesulfonyl-phenyl)propionic acid

Product 1

HCID 59331615HCID 59331615, compoundYield 28%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution (15 mL) of 3-cyclopentyl-2-[4-(methylsulfonyl)phenyl]propanoic acid (5.00 g) in dichloromethane were added oxalyl chloride (7.30 mL) and a catalytic amount of N,N-dimethylformamide under ice-cooling and the mixture was stirred for 30 min. The reaction mixture was concentrated, and the residue was dissolved in tetrahydrofuran (15 mL). Thereto was added triethylamine (9.4% mL) at room temperature, and the mixture was stirred for 30 min. The resulting precipitate was filtered off, enolate separately prepared from acetone (1.08 g) and potassium hydride (2.71 g: 30% wt) in tetrahydrofuran (15 mL) was added to the filtrate at −78° C., and the mixture was stirred for 1 hr. is The reaction mixture was slowly warmed to room temperature, and the mixture was stirred overnight. The reaction mixture was diluted with ethyl acetate, 1N hydrochloric acid was added and the mixture was stirred for 30 min. The ethyl acetate layer was washed with saturated brine, dried (MgSO4) and concentrated. The residue was subjected to preparative high performance liquid chromatography, and the title compound (1.60 g, yield 28%) was obtained as colorless amorphous crystals. MS: 337 (MH+).

Workup

  1. concentrationThe reaction mixture was concentrated
  2. dissolutionthe residue was dissolved in tetrahydrofuran (15 mL)
  3. additionThereto was added triethylamine (9.4% mL) at room temperature
  4. stirringthe mixture was stirred for 30 min
  5. filtrationThe resulting precipitate was filtered off
  6. customenolate separately prepared from acetone (1.08 g) and potassium hydride (2.71 g: 30% wt) in tetrahydrofuran (15 mL)
  7. additionwas added to the filtrate at −78° C.
  8. stirringthe mixture was stirred for 1 hr
  9. stirringthe mixture was stirred overnight
  10. additionwas added
  11. stirringthe mixture was stirred for 30 min
  12. washThe ethyl acetate layer was washed with saturated brine
  13. dry with materialdried (MgSO4)
  14. concentrationconcentrated

Sources & evidence

ORD record
ord-f8b8bbd7fa1e409baff665d82f73097a
Source dataset
uspto-grants-2012_11
Patent number
US08318746B2

Reaction notes

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