Sodium Acetate → tert-Butyl (2-cyclobutyl-1,5-dimethyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl)carbamate

HRID 1478216Notes

Reaction equation

HRID 1478216 reaction equation
[C:1]([O:5][C:6]([NH:8][C@@H:9]([C:14](=O)[CH3:15])[C:10]([O:12]C)=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH:17]1([NH:21][NH:22][CH3:23])[CH2:20][CH2:19][CH2:18]1.C([O-])(=O)C.[Na+]>CCOC(C)=O.O>[CH:17]1([N:21]2[C:10](=[O:12])[C:9]([NH:8][C:6](=[O:7])[O:5][C:1]([CH3:2])([CH3:3])[CH3:4])=[C:14]([CH3:15])[N:22]2[CH3:23])[CH2:20][CH2:19][CH2:18]1

Participants

6

Reactant 3

HCID 517045Sodium AcetateHCID 10561488(S)-Methyl 2-((tert-butoxycarbonyl)amino)-3-oxobutanoateHCID 1185110601-Cyclobutyl-2-methylhydrazine

Product 1

HCID 131736505tert-Butyl (2-cyclobutyl-1,5-dimethyl-3-oxo-2,3-dihydro-1H-pyrazol-4-yl)carbamate

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent2×

Conditions

Temperature
80 °C

Procedure

A solution of (S)-methyl 2-((tert-butoxycarbonyl)amino)-3-oxobutanoate (400 mg, 1.730 mmol) in EtOAc (6.407 mL) was treated with 1-cyclobutyl-2-methylhydrazine (284 mg, 2.076 mmol) followed by sodium acetate (213 mg, 2.59 mmol). The suspension was stirred at room temperature for 30 minutes and at 80° C. for 4 hours. The resulting mixture was diluted with water (10 mL) and EtOAc was added. The layers were separated and aqueous extracted with EtOAc. The combined organic layers were washed with brine, dried over MgSO4, filtered and the solvent removed under reduced pressure. The residue was dissolved in EtOAc and iso-hexane was added. The resulting suspension was filtered and the solid rinsed with iso-hexane. The filtrate was concentrated under reduced pressure. The crude material was then adsorbed onto silica and purification by chromatography eluting with 50-100% EtOAc in iso-hexane afforded the title compound;

Workup

  1. additionwas added
  2. customThe layers were separated
  3. extractionaqueous extracted with EtOAc
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried over MgSO4
  6. filtrationfiltered
  7. customthe solvent removed under reduced pressure
  8. dissolutionThe residue was dissolved in EtOAc
  9. additioniso-hexane was added
  10. filtrationThe resulting suspension was filtered
  11. washthe solid rinsed with iso-hexane
  12. concentrationThe filtrate was concentrated under reduced pressure
  13. customThe crude material was then adsorbed onto silica and purification by chromatography
  14. washeluting with 50-100% EtOAc in iso-hexane

Sources & evidence

ORD record
ord-404caa8cb85f4580a0eaf7bcfd0d4cff
Source dataset
uspto-grants-2016_08
Patent number
US09403810B2

Reaction notes

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