Acetic Acid → 2-chloro-4-[(2S,3S)-2-(cyclopropylmethyl)-3-hydroxy-5-oxopyrrolidin-1-yl]benzonitrile

HRID 1967411Notes

Reaction equation

HRID 1967411 reaction equation
[Cl:1][C:2]1[CH:9]=[C:8]([N:10]2[C:14](=[O:15])[CH:13]=[C:12]([OH:16])[CH:11]2[CH2:17][CH:18]2[CH2:20][CH2:19]2)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].C(O)(=O)C.[BH4-].[Na+].O>C(#N)C>[Cl:1][C:2]1[CH:9]=[C:8]([N:10]2[C:14](=[O:15])[CH2:13][C@H:12]([OH:16])[C@@H:11]2[CH2:17][CH:18]2[CH2:20][CH2:19]2)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 962WaterHCID 4311764Sodium borohydrideHCID 595569612-chloro-4-[2-(cyclopropylmethyl)-3-hydroxy-5-oxo-2,5-dihydro-1H-pyrrol-1-yl]benzonitrile

Product 1

HCID 595570292-chloro-4-[(2S,3S)-2-(cyclopropylmethyl)-3-hydroxy-5-oxopyrrolidin-1-yl]benzonitrileYield 77%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a mixture of 2-chloro-4-[2-(cyclopropylmethyl)-3-hydroxy-5-oxo-2,5-dihydro-1H-pyrrol-1-yl]benzonitrile (400 mg) and acetic acid (0.87 mL) in acetonitrile (10 mL) was added sodium borohydride (131 mg) at 0° C. in small portions. The mixture was warmed to room temperature and stirred for 1 hr. Water was added, and the mixture was extracted with ethyl acetate. The organic layer was washed with saturated brine, and dried over magnesium sulfate, and the solvent was evaporated under reduced pressure. The obtained residue was purified by basic silica gel column chromatography (eluent: hexane:ethyl acetate=4:1-3 ethyl acetate), and recrystallized from tetrahydrofuran-hexane to give the title compound as colorless crystals (yield: 310 mg, 77%).

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe organic layer was washed with saturated brine
  3. dry with materialdried over magnesium sulfate
  4. customthe solvent was evaporated under reduced pressure
  5. customThe obtained residue was purified by basic silica gel column chromatography (eluent: hexane:ethyl acetate=4:1-3 ethyl acetate)
  6. customrecrystallized from tetrahydrofuran-hexane

Sources & evidence

ORD record
ord-e8937dffd5b44a3d962b9b5ebfc48e95
Source dataset
uspto-grants-2013_04
Patent number
US08420694B2

Reaction notes

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