Trifluoroacetic acid → tert-butyl 4,5-dihydro-1H-pyrazole-5-carboxylate

HRID 1396883Notes

Reaction equation

HRID 1396883 reaction equation
[C:1]([O:5][C:6](=[O:9])[CH:7]=[CH2:8])([CH3:4])([CH3:3])[CH3:2].[Si]([CH:14]=[N+:15]=[N-:16])(C)(C)C.C(O)(C(F)(F)F)=O>C1(C)C=CC=CC=1.O1CCCC1.ClCCl>[NH:16]1[CH:7]([C:6]([O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[O:9])[CH2:8][CH:14]=[N:15]1

Participants

7

Reactant 3

HCID 6422Trifluoroacetic acidHCID 15458tert-Butyl acrylateHCID 167693Trimethylsilyldiazomethane

Product 1

HCID 86706338tert-butyl 4,5-dihydro-1H-pyrazole-5-carboxylateYield 60.3%

Reagents, catalysts & solvents 3

HCID 1140TolueneSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A 1 L rb flask was charged with t-butylacrylate (11.33 mL, 78 mmol) in toluene (100 mL) and tetrahydrofuran (THF) (100 mL). To this was added via addition funnel TMS-diazomethane (50.5 mL, 101 mmol) dropwise over 25 minutes under N2. The reaction mixture was stirred at 25° C. for 4.5 h. The solvent was evaporated under reduced pressure. The crude product was dissolved in dichloromethane (70 mL) and cooled in an ice bath. To this solution was added TFA (7.21 mL, 94 mmol.) dissolved in 30 mL of dichloromethane via addition funnel. After addition was complete the mixture was stirred at 25° C. for 0.5 h. The solvent was evaporated and the residue was neutralized by the addition of sat. NaHCO3 and extracted into DCM. The organic layer was dried over Na2SO4, filtered, and concentrated to give the crude product which was purified by automated silica gel column chromatography (column: 120 g, 0-38% ethyl acetate in hexane, 34 min). The solvent was removed under reduced pressure to afford 8 g (47 mmol, 60%) of 1,1-dimethylethyl 4,5-dihydro-1H-pyrazole-5-carboxylate as pale yellow oil. LC-MS (ES) m/e 171.1 (M+H)+.

Workup

  1. customThe solvent was evaporated under reduced pressure
  2. dissolutionThe crude product was dissolved in dichloromethane (70 mL)
  3. temperaturecooled in an ice bath
  4. additionAfter addition
  5. stirringwas stirred at 25° C. for 0.5 h
  6. customThe solvent was evaporated
  7. additionthe residue was neutralized by the addition of sat. NaHCO3
  8. extractionextracted into DCM
  9. dry with materialThe organic layer was dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customto give the crude product which
  13. customwas purified by automated silica gel column chromatography (column: 120 g, 0-38% ethyl acetate in hexane, 34 min)
  14. customThe solvent was removed under reduced pressure

Sources & evidence

ORD record
ord-f13529107d2641d7b6be7ea5178a59b6
Source dataset
uspto-grants-2014_12
Patent number
US08901119B2

Reaction notes

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