Ammonium Chloride → alpha-(1-Ethoxymethyl-5-pyrazolyl)-2,3-dichloro-4-hydroxybenzylalcohol

HRID 1721943Notes

Reaction equation

HRID 1721943 reaction equation
C([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:23]([Cl:24])=[C:22]([OH:25])[CH:21]=[CH:20][C:17]=1[CH:18]=[O:19].[Cl-].[NH4+]>CCCCCC.O1CCCC1.CN(C)P(=O)(N(C)C)N(C)C>[CH2:6]([O:8][CH2:9][N:10]1[C:14]([CH:18]([OH:19])[C:17]2[CH:20]=[CH:21][C:22]([OH:25])=[C:23]([Cl:24])[C:16]=2[Cl:15])=[CH:13][CH:12]=[N:11]1)[CH3:7]

Participants

8

Reactant 4

HCID 25517Ammonium ChlorideHCID 5283802,3-Dichloro-4-hydroxybenzaldehydeHCID 157143991-(ethoxymethyl)-1H-pyrazoleHCID 178418339Butyllithium

Product 1

HCID 14622794alpha-(1-Ethoxymethyl-5-pyrazolyl)-2,3-dichloro-4-hydroxybenzylalcoholYield 66.1%

Reagents, catalysts & solvents 3

HCID 8028TetrahydrofuranSolvent2×HCID 8058HexaneSolventHCID 12679HexamethylphosphoramideSolvent

Procedure

18.1 ml of 1.6M n-butyl lithium in hexane are added to a tetrahydrofuran solution of 3.56 g of 1-ethoxymethylpyrazole at -55° to -53° C. under argon gas atmosphere and the mixture is stirred at the same temperature for 1 hour. A solution of 2.45 g of 2,3-dichloro-4-hydroxybenzaldehyde in tetrahydrofuran is added to the above mixture, and the reaction mixture is stirred at -55° to -60° C. for 3 hours. 4.9 ml of hexamethylphosphoric triamide are then added and the whole mixture is stirred at room temperature for 16 hours. An aqueous saturated ammonium chloride solution is added and the mixture is extracted with ethyl acetate. The extract is washed with water, dried and evaporated to remove solvent. The residue is purified by silica gel column chromatography and crystallized with a mixture of ethyl acetate and isopropyl ether to give 2.69 g of α-(1-ethoxymethyl-5-pyrazolyl)-2,3-dichloro-4-hydroxybenzylalcohol.

Workup

  1. stirringthe reaction mixture is stirred at -55° to -60° C. for 3 hours
  2. stirringthe whole mixture is stirred at room temperature for 16 hours
  3. extractionthe mixture is extracted with ethyl acetate
  4. washThe extract is washed with water
  5. customdried
  6. customevaporated
  7. customto remove solvent
  8. customThe residue is purified by silica gel column chromatography
  9. customcrystallized with a mixture of ethyl acetate and isopropyl ether

Sources & evidence

ORD record
ord-4f8be800e3444e22a13b2dd6b1ad84df
Source dataset
uspto-grants-1989_08
Patent number
US04853404

Reaction notes

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