Acetic Anhydride → HCID 178489860, compound

HRID 2116477Notes

Reaction equation

HRID 2116477 reaction equation
[F:1][C:2]1[CH:3]=[C:4]([CH2:10][C:11]2[C:12](=[O:17])[NH:13][NH:14][C:15]=2[CH3:16])[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].[C:18](OC(=O)C)(=[O:20])[CH3:19]>C(O)(=O)C>[C:18]([N:14]1[C:15]([CH3:16])=[C:11]([CH2:10][C:4]2[CH:5]=[CH:6][C:7]([O:8][CH3:9])=[C:2]([F:1])[CH:3]=2)[C:12]([OH:17])=[N:13]1)(=[O:20])[CH3:19]

Participants

4

Reactant 2

HCID 7918Acetic AnhydrideHCID 22227667HCID 22227667, compound

Product 1

HCID 178489860HCID 178489860, compoundYield 20%

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
135 °C

Procedure

A mixture of 1,2-dihydro-4-[(3-fluoro-4-methoxyphenyl)methyl]-5-methyl-3H-pyrazol-3-one (synthesized as described in WO0236602; 4.11 g, 0.0174 mol), acetic anhydride (41 mL) and acetic acid (41 mL) was stirred at 135° C. for 8 hours and at room temperature for 12 hours. After being concentrated, the reaction mixture was diluted with toluene and then concentrated again. To the resulting residue, methanol (400 mL) and a 25 wt % methanol solution of sodium methoxide (0.37 mL) were added and stirred for 20 hours. The reaction mixture was concentrated and the resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1 to 1:1) to give 1-acetyl-4-[(3-fluoro-4-methoxyphenyl)methyl]-3-hydroxy-5-methyl-1H-pyrazole (960 mg, 20%) as a colorless powder.

Workup

  1. concentrationAfter being concentrated
  2. additionthe reaction mixture was diluted with toluene
  3. concentrationconcentrated again
  4. additionTo the resulting residue, methanol (400 mL) and a 25 wt % methanol solution of sodium methoxide (0.37 mL) were added
  5. stirringstirred for 20 hours
  6. concentrationThe reaction mixture was concentrated
  7. customthe resulting residue was purified by silica gel column chromatography (hexane:ethyl acetate=4:1 to 1:1)

Sources & evidence

ORD record
ord-815810224bb84ed0ba3081a2869856ae
Source dataset
uspto-grants-2008_10
Patent number
US07439232B2

Reaction notes

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