Ethyl Acetate → [5-(3,4-Dichlorophenyl)-1-(4-methoxyphenyl)-1H-pyrazol-3-yl]methanol

HRID 2376202Notes

Reaction equation

HRID 2376202 reaction equation
C([O:3][C:4]([C:6]1[CH:10]=[C:9]([C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[C:13]([Cl:18])[CH:12]=2)[N:8]([C:19]2[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=2)[N:7]=1)=O)C.[H-].C([Al+]CC(C)C)C(C)C.C(C(C(C([O-])=O)O)O)([O-])=O.[Na+].[K+].CCOC(C)=O>C1COCC1>[Cl:18][C:13]1[CH:12]=[C:11]([C:9]2[N:8]([C:19]3[CH:20]=[CH:21][C:22]([O:25][CH3:26])=[CH:23][CH:24]=3)[N:7]=[C:6]([CH2:4][OH:3])[CH:10]=2)[CH:16]=[CH:15][C:14]=1[Cl:17]

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 9855836Potassium sodium tartarateHCID 21225700DiisobutylaluminumhydrideHCID 21812731HCID 21812731, compound

Product 1

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

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of 5-(3,4-dichloro-phenyl)-1-(4-methoxy-phenyl)-1H-pyrazole-3-carboxylic acid ethyl ester (55.7 g, 0.140 mol) in THF (150 mL) at −78° C. under N2 was slowly added a 1.0 M solution of diisobutylaluminum hydride (DIBAL-H) (350 mL, 0.35 mol) over 45 min. The solution was allowed to stir for 20 min then warmed to rt over 90 min. The mixture was then cooled to 0° C., and a saturated solution of potassium sodium tartrate (300 mL) and EtOAc (400 mL) was added. The slurry mixture was stirred overnight whereupon both layers became clear. The organic layer was extracted with EtOAc (2×75 mL), dried with Na2SO4, filtered and concentrated. The crude product was dried under vacuum to recover 46.8 g (96%) of the title compound. This was used in the next step without further purification. HPLC: Rt=9.16 (Method E). MS (ES+): mass calculated for C17H14Cl2N2O2, 349.21; m/z found 371.1 [M+Na]+. 1H NMR (400 MHz, CDCl3): 7.39 (d, J=2.1 Hz, 1H), 7.34 (d, J=3.6 Hz, 1H), 7.20-7.09 (m, 2H), 6.97 (dd, J=8.36, 2.1 Hz,1H), 6.91-6.79 (m, 2H), 6.43 (s, 1H), 4.69 (s, 2H), 3.74 (s, 3H).

Workup

  1. temperatureThe mixture was then cooled to 0° C.
  2. stirringThe slurry mixture was stirred overnight whereupon both layers
  3. extractionThe organic layer was extracted with EtOAc (2×75 mL)
  4. dry with materialdried with Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. dry with materialThe crude product was dried under vacuum
  8. customto recover 46.8 g (96%) of the title compound
  9. customThis was used in the next step without further purification

Sources & evidence

ORD record
ord-2b728bda9e8b472ea4b15cafc6e99995
Source dataset
uspto-grants-2008_12
Patent number
US07465808B2

Reaction notes

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