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

HRID 2283649Notes

Reaction equation

HRID 2283649 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>[F:31][C:30]([F:32])([F:33])[C:28]1[CH:27]=[CH:26][C:25]([OH:34])=[C:24]([C:22]2[N:1]([CH:3]3[CH2:4][N:5]([C:7]([O:9][C:10]([CH3:13])([CH3:12])[CH3:11])=[O:8])[CH2:6]3)[N:2]=[CH:20][CH:21]=2)[CH:29]=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-carboxylateYield 64%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Procedure

To a stirred solution of crude tert-butyl 3-hydrazinoazetidine-1-carboxylate, (Preparation 31, 5.7 g, 0.03 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 33, 6.4 g, 24.7 mmol) was added portionwise and allowed to stir at ambient temperature for 20 hours. The reaction mixture was concentrated in vacuo and neutralised with aqueous sodium bicarbonate 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 afford the title compound as a white solid (7.4 g, 64%)

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-bf6f22eb4cf94353aa798fb7b280b4ee
Source dataset
uspto-grants-2015_09
Patent number
US09145407B2

Reaction notes

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