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

HRID 39442

Reaction equation

HRID 39442 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-40cedfe50bf042e2b18750b79218d9bb
Source dataset
uspto-grants-2013_09
Patent number
US08524910B2

Linked notes

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