4-Chlorobenzaldehyde → ethyl 4-((4-chlorophenyl)(hydroxy)methyl)-1-(4-methoxybenzyl)-5-methyl-1H-pyrazole-3-carboxylate

HRID 873793Notes

Reaction equation

HRID 873793 reaction equation
I[C:2]1[C:3]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[N:4][N:5]([CH2:8][C:9]2[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=2)[C:6]=1[CH3:7].[Cl:22][C:23]1[CH:30]=[CH:29][C:26]([CH:27]=[O:28])=[CH:25][CH:24]=1>C1COCC1>[Cl:22][C:23]1[CH:30]=[CH:29][C:26]([CH:27]([OH:28])[C:2]2[C:3]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[N:4][N:5]([CH2:8][C:9]3[CH:14]=[CH:13][C:12]([O:15][CH3:16])=[CH:11][CH:10]=3)[C:6]=2[CH3:7])=[CH:25][CH:24]=1

Participants

4

Reactant 2

HCID 77264-ChlorobenzaldehydeHCID 117702672ethyl 4-iodo-1-(4-methoxybenzyl)-5-methyl-1H-pyrazole-3-carboxylate

Product 1

HCID 117702762ethyl 4-((4-chlorophenyl)(hydroxy)methyl)-1-(4-methoxybenzyl)-5-methyl-1H-pyrazole-3-carboxylateYield 70%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of ethyl 4-iodo-1-(4-methoxybenzyl)-5-methyl-1H-pyrazole-3-carboxylate (Step 1.2) (6.23 g, 15.57 mmol) in THF (100 mL) under Ar was added TurboGrignard (15.57 mL, 20.24 mmol) at −10° C. After 15 min, 4-chlorobenzaldehyde (2.188 g, 15.57 mmol) was added. The reaction mixture was stirred for 30 min at this temperature, quenched with a saturated aqueous solution of NH4Cl (50 mL), extracted with EtOAc (2×50 mL). The combined organic layers were washed with a saturated aqueous solution of NH4Cl (75 mL), dried over Na2SO4 and evaporated. The crude material was purified by silica gel column chromatography (hexane/EtOAc 20-50%) to afford the title product (4.50 g, 10.85 mmol, 70% yield) as a colorless oil. tR: 5.34 min (HPLC 1); tR: 1.15 min (LC-MS 2); ESI-MS: 415 [M+H]+ (LC-MS 2); Rf=0.40 (hexane/EtOAc 1:1).

Workup

  1. customquenched with a saturated aqueous solution of NH4Cl (50 mL)
  2. extractionextracted with EtOAc (2×50 mL)
  3. washThe combined organic layers were washed with a saturated aqueous solution of NH4Cl (75 mL)
  4. dry with materialdried over Na2SO4
  5. customevaporated
  6. customThe crude material was purified by silica gel column chromatography (hexane/EtOAc 20-50%)

Sources & evidence

ORD record
ord-5acbb00ea01243b1bdc656bb131ae8ac
Source dataset
uspto-grants-2015_03
Patent number
US08975417B2

Reaction notes

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