Hydrochloric Acid → Methyl 5-cyano-5-[3-(cyclopentyloxy)-4-(difluoromethoxy)phenyl]-2-oxocyclohexanecarboxylate
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
Conditions
- Temperature
- 0 °C
Procedure
To a solution of dimethyl 4-cyano-4-(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.
Workup
- temperatureThe resulting mixture was refluxed for 20 min
- temperaturethe mixture was refluxed for another 70 min
- concentrationwas concentrated
- customThe mixture was partitioned between ether and dilute hydrochloric acid the organic layer
- dry with materialwas dried (magnesium sulfate)
- customthe solvent was removed in vacuo
- customThe product was purified by flash chromatography
- washeluting with 85:15 hexanes/ethyl acetate
Sources & evidence
- ORD record
- ord-cb6b37442aff43f7af4574c498f1a185
- Source dataset
- uspto-grants-1995_09
- Patent number
- US05449686
Reaction notes
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