Acetic Acid → tert-Butyl 3-[5-(5-trifluoromethyl-2-hydroxyphenyl)-1H-pyrazol-1-yl]azetidine-1-carboxylate

HRID 1402067Notes

Reaction equation

HRID 1402067 reaction equation
[NH:1]([CH:3]1[CH2:6][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:4]1)[NH2:2].C(O)(=O)C.CN(C)/[CH:20]=[CH:21]/[C:22]([C:24]1[CH:29]=[C:28]([C:30]([F:33])([F:32])[F:31])[CH:27]=[CH:26][C:25]=1[OH:34])=O>C(O)C>[OH:34][C:25]1[CH:26]=[CH:27][C:28]([C:30]([F:31])([F:32])[F:33])=[CH:29][C:24]=1[C:22]1[N:1]([CH:3]2[CH2:4][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:6]2)[N:2]=[CH:20][CH:21]=1

Participants

5

Reactant 3

HCID 176Acetic AcidHCID 58042291Tert-butyl 3-hydrazinylazetidine-1-carboxylateHCID 59436605(2E)-3-(dimethylamino)-1-[2-hydroxy-5-(trifluoromethyl)phenyl]prop-2-en-1-one

Product 1

HCID 136063628tert-Butyl 3-[5-(5-trifluoromethyl-2-hydroxyphenyl)-1H-pyrazol-1-yl]azetidine-1-carboxylate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a stirred solution of crude tert-butyl 3-hydrazinoazetidine-1-carboxylate, (Preparation 696, 5.7 g, 0.030 mol) in ethanol (66 mL) at 0° C. was added acetic acid (6.6 mL) dropwise. Then (2E)-3-(dimethylamino)-1-[2-hydroxy-5-(trifluoromethyl)phenyl]prop-2-en-1-one, (Preparation 859, 6.4 g, 24.68 m mol) was added portionwise and allowed to stir at room temperature for 20 hours. The reaction mixture was concentrated in vacuo and neutralised with aqueous sodium hydrogencarbonate solution. The mixture was extracted with ethyl acetate (150 mL). The combined organic layer was washed with water (100 mL), saturated aqueous sodium chloride solution (50 mL) and dried over anhydrous sodium sulphate. After concentration of organic layer in vacuo, the crude product was washed with 20% v/v ethyl acetate in hexane to get the title compound as a white solid (7.4 g)

Workup

  1. additionwas added portionwise
  2. concentrationThe reaction mixture was concentrated in vacuo
  3. extractionThe mixture was extracted with ethyl acetate (150 mL)
  4. washThe combined organic layer was washed with water (100 mL), saturated aqueous sodium chloride solution (50 mL)
  5. dry with materialdried over anhydrous sodium sulphate
  6. washAfter concentration of organic layer in vacuo, the crude product was washed with 20% v/v ethyl acetate in hexane

Sources & evidence

ORD record
ord-0e025e5af9284b2ea224b7ddad87b26e
Source dataset
uspto-grants-2014_12
Patent number
US08907101B2

Reaction notes

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