Methyl Acrylate → 5-Methoxy-3-(2-methoxycarbonyl-vinyl)-indazole-1-carboxylic acid tert-butyl ester

HRID 2064644Notes

Reaction equation

HRID 2064644 reaction equation
[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([O:17][CH3:18])=[CH:14][CH:15]=2)[C:10](I)=[N:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].C(N(CC)CC)C.[C:27]([O:31][CH3:32])(=[O:30])[CH:28]=[CH2:29].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[C:1]([O:5][C:6]([N:8]1[C:16]2[C:11](=[CH:12][C:13]([O:17][CH3:18])=[CH:14][CH:15]=2)[C:10]([CH:29]=[CH:28][C:27]([O:31][CH3:32])=[O:30])=[N:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 7294Methyl AcrylateHCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 20785164HCID 20785164, compound

Product 1

HCID 696182895-Methoxy-3-(2-methoxycarbonyl-vinyl)-indazole-1-carboxylic acid tert-butyl ester

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

A solution of 3-iodo-5-methoxy-indazole-1-carboxylic acid tert-butyl ester [0.500 g, Reference Example 22(a)] in dioxane (15 ml) and under an atmosphere of nitrogen was treated with triethylamine (1.86 ml) followed by methyl acrylate (1.20 ml), triphenylphosphine (0.105 g), and palladium (II) acetate (60 mg). The resulting mixture was heated at 50° C. for 16 hours, then cooled to ambient temperature and then evaporated. The residue was partitioned between ethyl acetate and water. The organic layer was washed with brine, then dried over magnesium sulfate and then evaporated. The residue was subjected to flash column chromatography on silica eluting with a mixture of ethyl acetate and 40/60 petrol (1:9, v/v) to yield 5-methoxy-3-(2-methoxycarbonyl-vinyl)-indazole-1-carboxylic acid tert-butyl ester (282 mg). LC-MS (METHOD B): RT=3.33 minutes; 333 (M+H)+.

Workup

  1. temperaturecooled to ambient temperature
  2. customevaporated
  3. customThe residue was partitioned between ethyl acetate and water
  4. washThe organic layer was washed with brine
  5. dry with materialdried over magnesium sulfate
  6. customevaporated
  7. additionThe residue was subjected to flash column chromatography on silica eluting with a mixture of ethyl acetate and 40/60 petrol (1:9, v/v)

Sources & evidence

ORD record
ord-fe8a5af570fc4ec181c92806a9de804e
Source dataset
uspto-grants-2012_10
Patent number
US08288425B2

Reaction notes

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