p-Toluenesulfonic acid monohydrate → HCID 67212603, compound

HRID 1671339Notes

Reaction equation

HRID 1671339 reaction equation
[CH2:1]([O:3][C:4]([C:6]1[C:7]([O:12][CH:13]([CH3:24])[C:14]([C:16]2[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][C:17]=2[CH3:23])=O)=[N:8][NH:9][C:10]=1[CH3:11])=[O:5])[CH3:2].O.C1(C)C=CC(S(O)(=O)=O)=CC=1>C1(C)C=CC=CC=1.CC(O)=O>[CH2:1]([O:3][C:4]([C:6]1[C:10]([CH3:11])=[N:9][N:8]2[C:14]([C:16]3[CH:21]=[CH:20][C:19]([CH3:22])=[CH:18][C:17]=3[CH3:23])=[C:13]([CH3:24])[O:12][C:7]=12)=[O:5])[CH3:2]

Participants

5

Reactant 2

HCID 521998p-Toluenesulfonic acid monohydrateHCID 178470036HCID 178470036, compound

Product 1

HCID 67212603HCID 67212603, compoundYield 88%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 1140TolueneSolvent

Procedure

A mixture of 3-[2-(2,4-dimethyl-phenyl)-1-methyl-2-oxo-ethoxy]-5-methyl-1H-pyrazole-4-carboxylic acid ethyl ester (273 mg, 0.83 mmol), para-toluenesulfonic acid mono-hydrate (160 mg, 0.83 mmol) in toluene (15 ml) and AcOH (5 ml) is refluxed for 3 days. The reaction mixture is concentrated in vacuo and the residue is dissolved in EtOAc (40 ml). The organic solution is washed successively with Na2CO3 2M in water (2×20 ml) and brine (20 ml), dried over Na2SO4, filtered and concentrated to dryness. The resulting crude residue is purified by Combi-Flash Companion™ (Isco Inc.) column chromatography (SiO2; gradient elution, iso-hexane/TBME 98:2→7:3) to yield the title compound (227 mg, 0.73 mmol, 88%) as a colorless oil. TLC: RF=0.81 (iso-hexane/TBME 1:1); HPLC: AtRet=2.85; MS: m/z 313.2 [M+H]+; 1H NMR (400 MHz, DMSO-d6) δ 1.30 (t, J 7.1, 3H), 2.20 (s, 3H), 2.34 (s, 3H), 2.36 (s, 3H), 2.41 (s, 3H), 4.26 (q, J 7.1, 2H), 7.17 (m, 1H), 7.24 (br. s., 1H), 7.31 (m, 1H).

Workup

  1. temperatureis refluxed for 3 days
  2. concentrationThe reaction mixture is concentrated in vacuo
  3. dissolutionthe residue is dissolved in EtOAc (40 ml)
  4. washThe organic solution is washed successively with Na2CO3 2M in water (2×20 ml) and brine (20 ml)
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customThe resulting crude residue is purified by Combi-Flash Companion™ (Isco Inc.) column chromatography (SiO2; gradient elution, iso-hexane/TBME 98:2→7:3)

Sources & evidence

ORD record
ord-8e681e4d263a4477b842c2f124bc5b99
Source dataset
uspto-grants-2011_08
Patent number
US07994203B2

Reaction notes

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