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

HRID 46378Notes

Reaction equation

HRID 46378 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 858, 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-07daa13e30e1450d927c1e6f62c9e81d
Source dataset
uspto-grants-2013_09
Patent number
US08541588B2

Reaction notes

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