p-Toluenesulfonic acid → [5-(3,4-Dichlorophenyl)-1-(4-methoxyphenyl)-1H-pyrazol-3-yl]methanol

HRID 2376254Notes

Reaction equation

HRID 2376254 reaction equation
C1(C)C=CC(S(O)(=O)=O)=CC=1.C1COCC1.CCOC(C)=O.[Cl:23][C:24]1[CH:25]=[C:26]([C:31]2[N:35]([C:36]3[CH:41]=[CH:40][C:39]([O:42][CH3:43])=[CH:38][CH:37]=3)[N:34]=[C:33]([CH2:44][O:45]C3CCCCO3)[CH:32]=2)[CH:27]=[CH:28][C:29]=1[Cl:30]>CO>[Cl:23][C:24]1[CH:25]=[C:26]([C:31]2[N:35]([C:36]3[CH:37]=[CH:38][C:39]([O:42][CH3:43])=[CH:40][CH:41]=3)[N:34]=[C:33]([CH2:44][OH:45])[CH:32]=2)[CH:27]=[CH:28][C:29]=1[Cl:30]

Participants

5

Reactant 3

HCID 6101p-Toluenesulfonic acidHCID 21939870Tetrahydrofuran ethyl acetateHCID 22170965HCID 22170965, compound

Product 1

HCID 22171056[5-(3,4-Dichlorophenyl)-1-(4-methoxyphenyl)-1H-pyrazol-3-yl]methanolYield 63.7%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A solution of p-toluenesulfonic acid (1.22 kg, 6.28 mol) in methanol (20.0 L) was added to the THF/EtOAc solution of 5-(3,4-dichlorophenyl)-1-(4-methoxyphenyl)-3-[[(tetrahydro-2H-pyran-2-yl)oxy]methyl]-1H-pyrazole (Example 515) at rt and the resulting mixture was stirred overnight (18 h). When HPLC analysis indicated the disappearance of the starting material, the reaction mixture was concentrated to remove methanol. The resulting mixture was washed with 10% aq. NaHCO3 (40.0 L) followed by brine (40.0 L). The organic layer was added to n-heptane and the resultant suspension was filtered, washed, and vacuum dried to afford [5-(3,4-dichlorophenyl)-1-(4-methoxyphenyl)-1H-pyrazol-3-yl]-methanol (4.65 kg, 63.7% over 3 chemical steps) as a solid. Data compared favorably with that obtained for Example 1, Step C.

Workup

  1. concentrationthe reaction mixture was concentrated
  2. customto remove methanol
  3. washThe resulting mixture was washed with 10% aq. NaHCO3 (40.0 L)
  4. additionThe organic layer was added to n-heptane
  5. filtrationthe resultant suspension was filtered
  6. washwashed
  7. customvacuum dried

Sources & evidence

ORD record
ord-bd881511f49c4bccb4040034edb285d4
Source dataset
uspto-grants-2008_12
Patent number
US07465808B2

Reaction notes

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