Dimethyl malonate → dimethyl 2-((1-(4-fluorophenyl)-1H-indazol-5-yl)methylene)malonate

HRID 563435Notes

Reaction equation

HRID 563435 reaction equation
[C:1]([O:8][CH3:9])(=[O:7])[CH2:2][C:3]([O:5][CH3:6])=[O:4].[F:10][C:11]1[CH:16]=[CH:15][C:14]([N:17]2[C:25]3[C:20](=[CH:21][C:22]([CH:26]=O)=[CH:23][CH:24]=3)[CH:19]=[N:18]2)=[CH:13][CH:12]=1>C1C=CC=CC=1.C(O)(=O)C>[F:10][C:11]1[CH:12]=[CH:13][C:14]([N:17]2[C:25]3[C:20](=[CH:21][C:22]([CH:26]=[C:2]([C:1]([O:8][CH3:9])=[O:7])[C:3]([O:5][CH3:6])=[O:4])=[CH:23][CH:24]=3)[CH:19]=[N:18]2)=[CH:15][CH:16]=1

Participants

5

Reactant 2

HCID 7943Dimethyl malonateHCID 579436121-(4-fluorophenyl)-1H-indazole-5-carbaldehyde

Product 1

HCID 67005843dimethyl 2-((1-(4-fluorophenyl)-1H-indazol-5-yl)methylene)malonateYield 87%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidCatalystHCID 241BenzeneSolvent

Procedure

To solution of dimethyl malonate (0.22 mL, 1.65 mmol) in benzene (15 mL) and acetic acid (3 drops) was added 1-(4-fluorophenyl)-1H-indazol-5-carboxaldehyde (330 mg, 1.38 mmol). The reaction mixture was heated at reflux overnight. The reaction was quenched with sat. KH2PO4 and extracted with EtOAc×3. The organic layers were dried over MgSO4, filtered, and concentrated. The residue was purified on SiO2 by MPLC using a 1:9 to 1:3 EtOAc/hexane gradient. Obtained 424 mg (87% yield) of dimethyl 2-((1-(4-fluorophenyl)-1H-indazol-5-yl)methylene)malonate. MS found: (M+H)+=355.

Workup

  1. temperatureThe reaction mixture was heated
  2. temperatureat reflux overnight
  3. customThe reaction was quenched with sat. KH2PO4
  4. extractionextracted with EtOAc×3
  5. dry with materialThe organic layers were dried over MgSO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified on SiO2 by MPLC

Sources & evidence

ORD record
ord-112af08f75a24044824f9683e5c2682e
Source dataset
uspto-grants-2011_11
Patent number
US08067447B2

Reaction notes

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