Hydrochloric Acid → HCID 178496137, compound

HRID 509610Notes

Reaction equation

HRID 509610 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:13]([OH:14])=[CH:12][C:11]([CH2:15][C:16]([O:18][CH3:19])=[O:17])=[N:10]1.[CH3:20][O:21][CH2:22][C:23](Cl)=[O:24].Cl>O1CCOCC1.[Cl-].[Na+].O>[Cl:1][C:2]1[CH:7]=[C:6]([F:8])[CH:5]=[CH:4][C:3]=1[N:9]1[C:13]([OH:14])=[C:12]([C:23](=[O:24])[CH2:22][O:21][CH3:20])[C:11]([CH2:15][C:16]([O:18][CH3:19])=[O:17])=[N:10]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 96623Methoxyacetyl chlorideHCID 178499533HCID 178499533, compound

Product 1

HCID 178496137HCID 178496137, compoundYield 74%

Reagents, catalysts & solvents 2

HCID 312751,4-DioxaneSolventHCID 57417360Sodium chloride; waterSolvent

Procedure

The mixture of the above obtained methyl [1-(2-chloro-4-fluorophenyl)-5-hydroxy-1H-pyrazol-3-yl]acetate (Compound of Formula (IV), 0.600 g, 2.11 mmol, 1 eq.), was suspended in dioxane (10 mL) and Ca(OH)2 (0.313 g, 4.22 mmol, 2eq.) and methoxyacetyl chloride (0.229 g, 2.11 mmol, 1 eq.) under nitrogen, was heated at 70° C. for 45-60 minutes. The resulting solution was concentrated in vacuo and the residue was partitioned between dichloromethane (50 ml) and a mixture of brine (10 ml) and 2N hydrochloric acid (1 ml, 2.00 mmol). The dichloromethane phase was collected. The aqueous phase was extracted with more dichloromethane (50 ml) and then ethyl acetate (50 ml). The combined organic phases were dried over Na2SO4 and the solvent evaporated to give methyl [1-(2-chloro-4-fluorophenyl)-5-hydroxy-4-(methoxyacetyl)-1H-pyrazol-3-yl]acetate as a beige solid (550 mg, 1.55 mmol, 74% yield, 92% HPLC) that can be used in the following step without further purification. MS(ESI+): 357.7; MS(ESI−): 355.8.

Workup

  1. additionThe mixture of the
  2. concentrationThe resulting solution was concentrated in vacuo
  3. customthe residue was partitioned between dichloromethane (50 ml)
  4. customThe dichloromethane phase was collected
  5. extractionThe aqueous phase was extracted with more dichloromethane (50 ml)
  6. dry with materialThe combined organic phases were dried over Na2SO4
  7. customthe solvent evaporated

Sources & evidence

ORD record
ord-267e2be031894d4985c21ca2b534f1dd
Source dataset
uspto-grants-2015_08
Patent number
US09096588B2

Reaction notes

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