Hydrochloric Acid → Methyl 4,5-dichloro-6-((1-ethoxymethyl-pyrazol-5-yl)-hydroxymethyl)-1,3-benzodioxole-2-carboxylate

HRID 1089159Notes

Reaction equation

HRID 1089159 reaction equation
[CH2:1]([Li])CCC.[CH2:6]([O:8][CH2:9][N:10]1[CH:14]=[CH:13][CH:12]=[N:11]1)[CH3:7].[Cl:15][C:16]1[C:24]2[O:23][CH:22]([C:25]([O-:27])=[O:26])[O:21][C:20]=2[CH:19]=[C:18]([CH:28]=[O:29])[C:17]=1[Cl:30].[Li+].[Cl-].[NH4+].Cl>CCCCCC.O1CCCC1.CN(C)P(=O)(N(C)C)N(C)C>[Cl:15][C:16]1[C:24]2[O:23][CH:22]([C:25]([O:27][CH3:1])=[O:26])[O:21][C:20]=2[CH:19]=[C:18]([CH:28]([C:14]2[N:10]([CH2:9][O:8][CH2:6][CH3:7])[N:11]=[CH:12][CH:13]=2)[OH:29])[C:17]=1[Cl:30]

Participants

9

Reactant 5

HCID 313Hydrochloric AcidHCID 25517Ammonium ChlorideHCID 157143991-(ethoxymethyl)-1H-pyrazoleHCID 23683076Lithium 4,5-dichloro-6-formyl-1,3-benzodioxole-2-carboxylateHCID 178418339Butyllithium

Product 1

HCID 15714401Methyl 4,5-dichloro-6-((1-ethoxymethyl-pyrazol-5-yl)-hydroxymethyl)-1,3-benzodioxole-2-carboxylateYield 75%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolventHCID 12679HexamethylphosphoramideSolvent

Procedure

A solution of 12.2 ml of 1.6M n-butyl lithium in hexane is added dropwise to a solution of 2.45 g of 1-ethoxymethyl-pyrazole in 50 ml of tetrahydrofuran at -60° to -50°) C. under argon gas atmosphere and the mixture is stirred at the same temperature for 40 minutes. A solution of 5.23 g of lithium 4,5-dichloro-6-formyl-1,3-benzodioxole-2-carboxylate in 40 ml of hexamethylphosphoric triamide is added dropwise to the reaction mixture at -60° to -50° C. and the mixture is stirred at the same temperature for 30 minutes. An aqueous saturated ammonium chloride solution and 1N hydrochloric acid are added to the reaction mixture, and the mixture is extracted with ethyl acetate. An excess amount of a solution of diazomethane in ether is added to the extract (the extract contains 4,5-dichloro-6-((1-ethoxymethyl-pyrazol-5-yl)-hydroxymethyl)-1,3-benzodioxole-2-carbo xylic acid) and the mixture is stirred for 10 minutes. The mixture is evaporated to remove solvent and the residue is purified by silica gel column chromatography (solvent: chloroform-acetone-ethanol) to give 5.9 g of methyl 4,5-dichloro-6-((1-ethoxymethyl-pyrazol-5-yl)-hydroxymethyl) -1,3-benzodioxole-2-carboxylate (a mixture of diastereoisomers thereof) as an oil. Yield: 75%

Workup

  1. stirringthe mixture is stirred at the same temperature for 30 minutes
  2. extractionthe mixture is extracted with ethyl acetate
  3. additionAn excess amount of a solution of diazomethane in ether is added to the
  4. extractionextract (the extract
  5. stirringis stirred for 10 minutes
  6. customThe mixture is evaporated
  7. customto remove solvent
  8. customthe residue is purified by silica gel column chromatography (solvent: chloroform-acetone-ethanol)

Sources & evidence

ORD record
ord-d01e6696fc004afca878a19f5f463bd9
Source dataset
uspto-grants-1990_10
Patent number
US04965282

Reaction notes

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