Sodium hydride → Methyl 5-[3,4-bis(difluoromethoxy)phenyl]-5-cyano-2-oxocyclohexanecarboxylate

HRID 1451925Notes

Reaction equation

HRID 1451925 reaction equation
[F:1][CH:2]([F:29])[O:3][C:4]1[CH:5]=[C:6]([C:14]([C:27]#[N:28])([CH2:21][CH2:22][C:23](OC)=[O:24])[CH2:15][CH2:16][C:17]([O:19][CH3:20])=[O:18])[CH:7]=[CH:8][C:9]=1[O:10][CH:11]([F:13])[F:12].[H-].[Na+]>COCCOC>[C:17]([CH:16]1[CH2:15][C:14]([C:6]2[CH:7]=[CH:8][C:9]([O:10][CH:11]([F:12])[F:13])=[C:4]([O:3][CH:2]([F:29])[F:1])[CH:5]=2)([C:27]#[N:28])[CH2:21][CH2:22][C:23]1=[O:24])([O:19][CH3:20])=[O:18]

Participants

4

Reactant 2

HCID 24758Sodium hydrideHCID 18973712HCID 18973712, compound

Product 1

HCID 15293895Methyl 5-[3,4-bis(difluoromethoxy)phenyl]-5-cyano-2-oxocyclohexanecarboxylateYield 46.8%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent

Procedure

To a solution of dimethyl 4-(3,4-bisdifluoromethoxyphenyl)-4-cyanopimelate (45.32 g, 107 mmol) in dry 1,2-dimethoxyethane (450 mL) under an argon atmosphere was added sodium hydride (80% dispersion in mineral oil, 13 g, 432 mmol). The resulting mixture was refluxed for 1 h, was cooled to room temperature was quenched with water and was concentrated. The mixture was partitioned between ether and acidic brine, was extracted twice with ether, the organic layer was dried (magnesium sulfate) and the solvent was removed in vacuo. The residue was purified by flash chromatography, eluting with 3:1 hexanes/ethyl acetate, to provide a pale-orange oil (19.5 g, 46.6%).

Workup

  1. temperatureThe resulting mixture was refluxed for 1 h
  2. customwas quenched with water
  3. concentrationwas concentrated
  4. customThe mixture was partitioned between ether and acidic brine
  5. extractionwas extracted twice with ether
  6. dry with materialthe organic layer was dried (magnesium sulfate)
  7. customthe solvent was removed in vacuo
  8. customThe residue was purified by flash chromatography
  9. washeluting with 3:1 hexanes/ethyl acetate

Sources & evidence

ORD record
ord-1ffa8e761d0c4c32b70f9dbbf1fa5415
Source dataset
uspto-grants-1997_02
Patent number
US05605923

Reaction notes

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