Acetonitrile → 1,3-Benzodioxole-5-carboxylic acid, 2,2-difluoro-, methyl ester

HRID 401510Notes

Reaction equation

HRID 401510 reaction equation
Br[C:2]1[CH:12]=[CH:11][C:5]2[O:6][C:7]([F:10])([F:9])[O:8][C:4]=2[CH:3]=1.C(#N)C.C(N(CC)CC)C>CO.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH3:5][O:6][C:7]([C:2]1[CH:12]=[CH:11][C:5]2[O:6][C:7]([F:10])([F:9])[O:8][C:4]=2[CH:3]=1)=[O:8]

Participants

6

Reactant 3

HCID 6342AcetonitrileHCID 8471TriethylamineHCID 27362715-Bromo-2,2-difluoro-1,3-benzodioxole

Product 1

HCID 591292611,3-Benzodioxole-5-carboxylic acid, 2,2-difluoro-, methyl esterYield 212.8%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolvent

Conditions

Temperature
75 °C

Procedure

A solution of 5-bromo-2,2-difluoro-benzo[1,3]dioxole (11.8 g, 50.0 mmol) and tetrakis(triphenylphosphine)palladium (0) [Pd(PPh3)4, 5.78 g, 5.00 mmol] in methanol (20 mL) containing acetonitrile (30 mL) and triethylamine (10 mL) was stirred under a carbon monoxide atmosphere (55 PSI) at 75° C. (oil bath temperature) for 15 hours. The cooled reaction mixture was filtered and the filtrate was evaporated to dryness. The residue was purified by silica gel column chromatography to give crude 2,2-difluoro-benzo[1,3]dioxole-5-carboxylic acid methyl ester (11.5 g), which was used directly in the next step.

Workup

  1. customThe cooled reaction mixture
  2. filtrationwas filtered
  3. customthe filtrate was evaporated to dryness
  4. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-6cf3e87ffadc458d9295024cad4f6466
Source dataset
uspto-grants-2014_06
Patent number
US08741933B2

Reaction notes

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