Tributylphosphine → (3R)-3-methyl-1-(1-methyl-1H-pyrazol-3-yl)pyrrolidin-2-one

HRID 632796Notes

Reaction equation

HRID 632796 reaction equation
O[CH2:2][CH2:3][C@@H:4]([CH3:14])[C:5]([NH:7][C:8]1[CH:12]=[CH:11][N:10]([CH3:13])[N:9]=1)=[O:6].C(P(CCCC)CCCC)CCC.C1(C)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>C1COCC1.C(OCC)(=O)C>[CH3:14][C@@H:4]1[CH2:3][CH2:2][N:7]([C:8]2[CH:12]=[CH:11][N:10]([CH3:13])[N:9]=2)[C:5]1=[O:6]

Participants

6

Reactant 3

HCID 13831TributylphosphineHCID 66777355Diethylazodicarboxylate tolueneHCID 118060904(2R)-4-hydroxy-2-methyl-N-(1-methyl-1H-pyrazol-3-yl)butanamide

Product 1

HCID 118061232(3R)-3-methyl-1-(1-methyl-1H-pyrazol-3-yl)pyrrolidin-2-oneYield 49.4%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (2R)-4-hydroxy-2-methyl-N-(1-methyl-1H-pyrazol-3-yl)butanamide (216 mg) and tri-n-butylphosphine (0.54 mL) in THF (10 mL) was added 40% diethyl azodicarboxylate toluene solution (1.0 mL). The reaction mixture was stirred at room temperature for 15 hr, and diluted with ethyl acetate. The diluted solution was washed with saturated brine, and dried over anhydrous sodium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane), and then HPLC (C18, mobile phase: water/acetonitrile (containing 0.1% TFA)), and to the obtained fraction was added ethyl acetate. The mixture was washed with saturated aqueous sodium carbonate solution and saturated brine, and dried over anhydrous sodium sulfate, and the solvent was concentrated under reduced pressure to give the title compound (97 mg).

Workup

  1. washThe diluted solution was washed with saturated brine
  2. dry with materialdried over anhydrous sodium sulfate
  3. customthe solvent was evaporated under reduced pressure
  4. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)
  5. additionHPLC (C18, mobile phase: water/acetonitrile (containing 0.1% TFA)), and to the obtained fraction was added ethyl acetate
  6. washThe mixture was washed with saturated aqueous sodium carbonate solution and saturated brine
  7. dry with materialdried over anhydrous sodium sulfate
  8. concentrationthe solvent was concentrated under reduced pressure

Sources & evidence

ORD record
ord-20af8da5ff0a4a53bd11b72452bd23bf
Source dataset
uspto-grants-2016_04
Patent number
US09321757B2

Reaction notes

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