Ethyl Acetate → N-(4-hydroxy-3-(2-methyl-2H-pyrazol-3-yl)phenyl)acetamide

HRID 407486Notes

Reaction equation

HRID 407486 reaction equation
C[O:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:12])[CH3:11])=[CH:5][C:4]=1[C:13]1[N:14]([CH3:18])[N:15]=[CH:16][CH:17]=1.[Cl-].[Al+3].[Cl-].[Cl-].C(OCC)(=O)C>ClCCCl>[OH:2][C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:12])[CH3:11])=[CH:5][C:4]=1[C:13]1[N:14]([CH3:18])[N:15]=[CH:16][CH:17]=1

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 6451240Aluminum(III) ChlorideHCID 59514683(N-[4-methoxy-3-(2-methyl-2H-pyrazol-3-yl)phenyl])acetamide

Product 1

HCID 135697938N-(4-hydroxy-3-(2-methyl-2H-pyrazol-3-yl)phenyl)acetamideYield 70%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Conditions

Temperature
0 °C

Procedure

A mixture of N-[4-methoxy-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-acetamide (2.0 g, 8.15 mmol) in anhydrous 1,2-dichloroethane (60 mL) was cooled at 0° C. on an ice bath and stirred for 10 minutes. Anhydrous aluminium chloride (4.35 g, 32.6 mmol) was added and the reaction mixture stirred at 0° C. for 20 minutes, then moved to an oil bath and stirred at 80° C. for 1 hour. Ethyl acetate was added and washed with potassium sodium tartrate (10%) twice. Organic layer was separated, dried over anhydrous Na2SO4, filtered and concentrated to give a crude product that was purified via preparative HPLC. The corresponding fractions were collected and lyophilized to afford N-[4-hydroxy-3-(2-methyl-2H-pyrazol-3-yl)-phenyl]-acetamide as a white solid in 70.0% yield. LCMS m/z (%)=232 (M+H, 100). 1H NMR (400 MHz, DMSO-d6) δ: 7.39 (s, 1H), 6.86 (d, J=8.74 Hz, 1H), 6.62 (d, J=8.70 Hz, 1H), 6.47 (s, 1H), 6.15 (s, 1H), 4.80 (bs, 2H), 3.87 (t, J=5.80 Hz, 2H), 3.63 (s, 3H), 2.44 (t, J=5.80 Hz, 2H), 2.08 (s, 6H).

Workup

  1. stirringthe reaction mixture stirred at 0° C. for 20 minutes
  2. custommoved to an oil bath
  3. stirringstirred at 80° C. for 1 hour
  4. washwashed with potassium sodium tartrate (10%) twice
  5. customOrganic layer was separated
  6. dry with materialdried over anhydrous Na2SO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give a crude product that
  10. customwas purified via preparative HPLC
  11. customThe corresponding fractions were collected

Sources & evidence

ORD record
ord-ab95b345d44c49a6bd66ce6cfc127f50
Source dataset
uspto-grants-2014_06
Patent number
US08754238B2

Reaction notes

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