4-Chlorobenzaldehyde → ethyl 4-((4-chlorophenyl)(hydroxy)methyl)-1-methyl-1H-pyrazole-3-carboxylate

HRID 873808Notes

Reaction equation

HRID 873808 reaction equation
I[C:2]1[C:3]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[N:4][NH:5][CH:6]=1.[Cl:12][C:13]1[CH:20]=[CH:19][C:16]([CH:17]=[O:18])=[CH:15][CH:14]=1.[CH2:21]1COCC1>>[Cl:12][C:13]1[CH:20]=[CH:19][C:16]([CH:17]([OH:18])[C:2]2[C:3]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[N:4][N:5]([CH3:21])[CH:6]=2)=[CH:15][CH:14]=1

Participants

4

Reactant 3

HCID 77264-ChlorobenzaldehydeHCID 8028TetrahydrofuranHCID 178470493HCID 178470493, compound

Product 1

HCID 117702817ethyl 4-((4-chlorophenyl)(hydroxy)methyl)-1-methyl-1H-pyrazole-3-carboxylateYield 82%

Procedure

To a stirred solution of ethyl 4-iodo-1H-pyrazole-3-carboxylate (Step 10.1) (2 g, 7.14 mmol) in THF (40 mL) under Ar was added TurboGrignard (5.77 mL, 7.50 mmol) at −10° C. After 30 min, 4-chlorobenzaldehyde (1.004 g, 7.14 mmol) was added. The reaction mixture was stirred for 60 min at rt, quenched with a saturated aq. NH4Cl solution, and extracted EtOAc. The combined organic layers were washed a saturated aq. NH4Cl solution, dried over Na2SO4 and evaporated. The crude material was purified by silica gel column chromatography (hexane/EtOAc 35-55%) to afford the title product (1.73 g, 5.87 mmol, 82% yield) as a colorless oil. tR: 4.10 min (HPLC 1); tR: 0.89 min (LC-MS 2); ESI-MS: 277/279 [M-18] (LC-MS 2); Rf=0.15 (hexane/EtOAc 1:1).

Workup

  1. customquenched with a saturated aq. NH4Cl solution
  2. extractionextracted EtOAc
  3. washThe combined organic layers were washed a saturated aq. NH4Cl solution
  4. dry with materialdried over Na2SO4
  5. customevaporated
  6. customThe crude material was purified by silica gel column chromatography (hexane/EtOAc 35-55%)

Sources & evidence

ORD record
ord-a32ff3909bdb4040b67906bd69396a31
Source dataset
uspto-grants-2015_03
Patent number
US08975417B2

Reaction notes

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