Water → 2-(4-Benzyloxy-3,5-difluoro-phenyl)-cyclopropane-carboxylic acid ethyl ester

HRID 62876Notes

Reaction equation

HRID 62876 reaction equation
[CH2:1]([O:3][C:4](=[O:23])/[CH:5]=[CH:6]/[C:7]1[CH:12]=[C:11]([F:13])[C:10]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:9]([F:22])[CH:8]=1)[CH3:2].[N+](=[CH2:26])=[N-].O>C1COCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([O:3][C:4]([CH:5]1[CH2:26][CH:6]1[C:7]1[CH:12]=[C:11]([F:13])[C:10]([O:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)=[C:9]([F:22])[CH:8]=1)=[O:23])[CH3:2]

Participants

6

Reactant 3

HCID 962WaterHCID 9550DiazomethaneHCID 90118234(E)-3-(4-benzyloxy-3,5-difluoro-phenyl)-acrylic acid ethyl ester

Product 1

HCID 594198442-(4-Benzyloxy-3,5-difluoro-phenyl)-cyclopropane-carboxylic acid ethyl esterYield 87%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolvent

Procedure

After (E)-3-(4-benzyloxy-3,5-difluoro-phenyl)-acrylic acid ethyl ester (2.5 g, 7.85 mmol) obtained in Step C of Preparation Example 2 was dissolved in THF (10 mL), diazomethane solution (94 mL, 23.55 mmol, 0.25M ether) was added thereto. After the reactant was cooled to 0˜5° C., palladium(II) acetate (0.29 g, 1.30 mmol) was added slowly thereto, and the mixture was stirred at room temperature for 5 hours. After the termination of the reaction, the reactant was added with water and then extracted. The organic layer was concentrated under reduced pressure and the residue was purified by column chromatography (eluent EtOAc/Hex=1/10) to obtain the title compound (2.27 g, 87%).

Workup

  1. temperatureAfter the reactant was cooled to 0˜5° C.
  2. customAfter the termination of the reaction
  3. extractionextracted
  4. concentrationThe organic layer was concentrated under reduced pressure
  5. customthe residue was purified by column chromatography (eluent EtOAc/Hex=1/10)

Sources & evidence

ORD record
ord-d19121caef5d4bf2970c990b31d735f1
Source dataset
uspto-grants-2016_09
Patent number
US09447044B2

Reaction notes

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