Silane, ((1-methoxy-2-methyl-1-propenyl)oxy)trimethyl- → methyl 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-3-hydroxy-2,2-dimethylpropanoate

HRID 563417Notes

Reaction equation

HRID 563417 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([CH:17]=[O:18])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:4][CH:3]=1.[CH3:19][O:20][C:21]([O:25][Si](C)(C)C)=[C:22]([CH3:24])[CH3:23]>C(Cl)Cl.Cl[Ti](Cl)(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[C:16]3[C:11](=[CH:12][C:13]([CH:17]([OH:18])[C:22]([CH3:24])([CH3:23])[C:21]([O:20][CH3:19])=[O:25])=[CH:14][CH:15]=3)[CH:10]=[N:9]2)=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 552336Silane, ((1-methoxy-2-methyl-1-propenyl)oxy)trimethyl-HCID 579436121-(4-fluorophenyl)-1H-indazole-5-carbaldehyde

Product 1

HCID 67005676methyl 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-3-hydroxy-2,2-dimethylpropanoateYield 50%

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 6344DichloromethaneSolvent

Procedure

To solution of 1-(4-fluorophenyl)-1H-indazol-5-carboxaldehyde (1.0 g, 4.16 mmol) and 1-methoxy-2-methyl-1-(trimethylsiloxy)propene (0.85 mL, 4.2 mmol) in 10 mL of dry DCM at 0° C. was added TiCl4 (0.8 mL of 1.0 M DCM solution, 0.8 mmol) The reaction was stirred 2 h and then quenched with aqueous sodium bicarbonate and extracted 2×EtOAc. The organic layers were dried over MgSO4, filtered, and concentrated. The residue was purified by SiO2 chromatography eluting with 1:2 EtOAc/hexane to give 700 mg (50% yield) of methyl 3-(1-(4-fluorophenyl)-1H-indazol-5-yl)-3-hydroxy-2,2-dimethylpropanoate. MS found: (M+H)+=343.

Workup

  1. customquenched with aqueous sodium bicarbonate
  2. extractionextracted 2×EtOAc
  3. dry with materialThe organic layers were dried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by SiO2 chromatography
  7. washeluting with 1:2 EtOAc/hexane

Sources & evidence

ORD record
ord-7f53444698444336b429b6e2a9bcb6dc
Source dataset
uspto-grants-2011_11
Patent number
US08067447B2

Reaction notes

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