Dimethylformamide → 7-(4,4,4-Trifluoro-1,1-dimethyl-3-oxobutyl)-2,3-dihydrobenzofuran-5-carbonitrile

HRID 916019Notes

Reaction equation

HRID 916019 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:11]([CH3:20])([CH3:19])[CH2:12][C:13](=[O:18])[C:14]([F:17])([F:16])[F:15])[C:5]2[O:9][CH2:8][CH2:7][C:6]=2[CH:10]=1.[CH3:21][N:22](C=O)C>[Cl-].[NH4+].[C-]#N.[Zn+2].[C-]#N.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>[F:15][C:14]([F:17])([F:16])[C:13](=[O:18])[CH2:12][C:11]([C:4]1[C:5]2[O:9][CH2:8][CH2:7][C:6]=2[CH:10]=[C:2]([C:21]#[N:22])[CH:3]=1)([CH3:20])[CH3:19]

Participants

6

Reactant 2

HCID 6228DimethylformamideHCID 223986074-(5-Bromo-2,3-dihydrobenzofuran-7-yl)-1,1,1-trifluoro-4-methylpentan-2-one

Product 1

HCID 694750267-(4,4,4-Trifluoro-1,1-dimethyl-3-oxobutyl)-2,3-dihydrobenzofuran-5-carbonitrileYield 60%

Reagents, catalysts & solvents 3

HCID 11186Zinc cyanide (Zn(CN)2)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 25517Ammonium ChlorideSolvent

Conditions

Temperature
130 °C

Procedure

A mixture of 201 mg (0.57 mmol) of the above 4-(5-bromo-2,3-dihydrobenzofuran-7-yl)-1,1,1-trifluoro-4-methylpentan-2-one, 144 mg (1.22 mmol) of zinc cyanide and 24 mg (0.021 mmol) of tetrakis(triphenylphosphine)palladium(0) in 2 mL of DMF was warmed at 130° C. After 36 hours, the mixture was cooled, diluted with 10 mL of saturated aqueous ammonium chloride, and extracted with three 7 mL portions EtOAc. The combined organic layers were washed with three 7 mL portions of brine, dried over magnesium sulfate, filtered, and concentrated in vacuo. The residue was adsorbed onto silica gel and chromatographed on silica gel using EtOAc-hexanes (0:100, then 1:99, then 2:98, then 3:97, then 4:96) to afford 102 mg (60%) of 7-(4,4,4-trifluoro-1,1-dimethyl-3-oxobutyl)-2,3-dihydrobenzofuran-5-carbonitrile as a white solid.

Workup

  1. temperaturethe mixture was cooled
  2. extractionextracted with three 7 mL portions EtOAc
  3. washThe combined organic layers were washed with three 7 mL portions of brine
  4. dry with materialdried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. customchromatographed on silica gel

Sources & evidence

ORD record
ord-78376683f2de49c8b01803d8e5088d29
Source dataset
uspto-grants-2007_09
Patent number
US07268152B2

Reaction notes

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