Acetic Acid → 2-[[[(1-{6-[(2,2-Dichlorocyclopropyl)methoxy]-5-fluoro-1-methylindazol-3-yl}ethylidene)amino]oxy]methyl]-alpha-(methoxymethylene)phenylacetic Acid Methyl Ester

HRID 1584714

Reaction equation

HRID 1584714 reaction equation
[Cl:1][C:2]1([Cl:22])[CH2:4][CH:3]1[CH2:5][O:6][C:7]1[CH:15]=[C:14]2[C:10]([C:11]([C:17](=[N:19][OH:20])[CH3:18])=[N:12][N:13]2[CH3:16])=[CH:9][C:8]=1[F:21].[H-].[Na+].[CH3:25][O:26][C:27](=[O:40])[C:28]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=1[CH2:38]Br)=[CH:29][O:30][CH3:31].C(O)(=O)C>CN(C)C=O>[CH3:25][O:26][C:27](=[O:40])[C:28]([C:32]1[CH:37]=[CH:36][CH:35]=[CH:34][C:33]=1[CH2:38][O:20][N:19]=[C:17]([C:11]1[C:10]2[C:14](=[CH:15][C:7]([O:6][CH2:5][CH:3]3[CH2:4][C:2]3([Cl:1])[Cl:22])=[C:8]([F:21])[CH:9]=2)[N:13]([CH3:16])[N:12]=1)[CH3:18])=[CH:29][O:30][CH3:31]

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 24758Sodium hydrideHCID 53395349Methyl 2-[2-(bromomethyl)phenyl]-3-methoxyprop-2-enoateHCID 1363407281-[6-(2,2-dichlorocyclopropylmethoxy)-5-fluoro-1-methyl-1H-indazol-3-yl]-ethanone oxime

Product 1

HCID 867543822-[[[(1-{6-[(2,2-Dichlorocyclopropyl)methoxy]-5-fluoro-1-methylindazol-3-yl}ethylidene)amino]oxy]methyl]-alpha-(methoxymethylene)phenylacetic Acid Methyl Ester

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent3×

Procedure

A solution of 0.9 g of 1-[6-(2,2-dichlorocyclopropylmethoxy)-5-fluoro-1-methyl-1H-indazol-3-yl]-ethanone oxime in 10 ml of N,N-dimethylformamide is added dropwise to a suspension of 0.2 g of sodium hydride in 15 ml of N,N-dimethylformamide and the reaction mixture is stirred at room temperature for 15 minutes. Then 1.04 g of 2-(α-bromo-o-tolyl)-3-methoxyacrylic acid methyl ester in 10 ml of N,N-dimethylformamide are added dropwise and the reaction mixture is stirred at room temperature for a further 3 hours. The mixture is then acidified with acetic acid and concentrated by evaporation in vacuo at approx. 50° C. The residue is dissolved in ethyl acetate and the solution is washed twice with water and once with saturated sodium chloride solution, dried with sodium sulfate and concentrated by evaporation in vacuo. Purification by flash chromatography (silica gel, ethyl acetate/hexane 1:1) yields the title compound having a melting point of 138-140° C.

Workup

  1. stirringthe reaction mixture is stirred at room temperature for a further 3 hours
  2. concentrationconcentrated by evaporation in vacuo at approx. 50° C
  3. dissolutionThe residue is dissolved in ethyl acetate
  4. washthe solution is washed twice with water and once with saturated sodium chloride solution
  5. dry with materialdried with sodium sulfate
  6. concentrationconcentrated by evaporation in vacuo
  7. customPurification by flash chromatography (silica gel, ethyl acetate/hexane 1:1)

Sources & evidence

ORD record
ord-e38432dbd68c4e1d87c34b8cdedadc95
Source dataset
uspto-grants-1999_08
Patent number
US05935908

Linked notes

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