Hydrochloric Acid → Methyl 5-cyano-5-[3-(cyclopentyloxy)-4-(difluoromethoxy)phenyl]-2-oxocyclohexanecarboxylate

HRID 1780837Notes

Reaction equation

HRID 1780837 reaction equation
[C:1]([C:3]([C:16]1[CH:21]=[CH:20][C:19]([O:22][CH:23]([F:25])[F:24])=[C:18]([O:26][CH:27]2[CH2:31][CH2:30][CH2:29][CH2:28]2)[CH:17]=1)([CH2:10][CH2:11][C:12]([O:14][CH3:15])=[O:13])[CH2:4][CH2:5][C:6]([O:8]C)=O)#[N:2].[H-].[Na+].Cl>COCCOC>[C:12]([CH:11]1[CH2:10][C:3]([C:1]#[N:2])([C:16]2[CH:21]=[CH:20][C:19]([O:22][CH:23]([F:24])[F:25])=[C:18]([O:26][CH:27]3[CH2:31][CH2:30][CH2:29][CH2:28]3)[CH:17]=2)[CH2:4][CH2:5][C:6]1=[O:8])([O:14][CH3:15])=[O:13]

Participants

5

Reactant 3

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 18973692HCID 18973692, compound

Product 1

HCID 10364019Methyl 5-cyano-5-[3-(cyclopentyloxy)-4-(difluoromethoxy)phenyl]-2-oxocyclohexanecarboxylateYield 37%

Reagents, catalysts & solvents 1

HCID 80711,2-DimethoxyethaneSolvent2×

Conditions

Temperature
0 °C

Procedure

To a solution of dimethyl 4-cyano4-(3-cyclopentyloxy-4-difluoromethoxyphenyl)pimelate (3.1 g, 6.7 mmol) in dry 1,2-dimethoxyethane (50 mL) under an argon atmosphere was added sodium hydride (80% dispersion in mineral oil, 0.81 g, 27 mmol). The resulting mixture was refluxed for 20 min, additional 1,2-dimethoxyethane (50 mL) was added and the mixture was refluxed for another 70 min. The mixture was cooled to 0° C., was acidified with dilute hydrochloric acid and was concentrated The mixture was partitioned between ether and dilute hydrochloric acid, the organic layer was dried (magnesium sulfate) and the solvent was removed in vacuo. The product was purified by flash chromatography, eluting with 85:15 hexanes/ethyl acetate, to provide a white solid (0.76 g, 37%): m.p. 109°-110.5° C. Analysis Calc. for C21H23F2NO5 : C 61.91, H 5.69, N 3.44; found: C 61.83, H 5.66, N 3.39.

Workup

  1. temperatureThe resulting mixture was refluxed for 20 min
  2. temperaturethe mixture was refluxed for another 70 min
  3. concentrationwas concentrated The mixture
  4. customwas partitioned between ether and dilute hydrochloric acid
  5. dry with materialthe organic layer was dried (magnesium sulfate)
  6. customthe solvent was removed in vacuo
  7. customThe product was purified by flash chromatography
  8. washeluting with 85:15 hexanes/ethyl acetate

Sources & evidence

ORD record
ord-0e024d2a3d134e73a379f1c7cd79c523
Source dataset
uspto-grants-1997_05
Patent number
US05631286

Reaction notes

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