1,2-Dimethoxyethane → 3-(Cyclopropylmethoxy)-4-(difluoromethoxy)benzaldehyde
Reaction equation
[H-].[Na+].C([C:5]([C:18]1[CH:23]=[CH:22][C:21]([O:24][CH:25]([F:27])[F:26])=[C:20]([O:28][CH2:29][CH:30]2[CH2:32][CH2:31]2)[CH:19]=1)(CCC(OC)=O)CCC(OC)=O)#N.C[O:34]CCOC>>[CH:30]1([CH2:29][O:28][C:20]2[CH:19]=[C:18]([CH:23]=[CH:22][C:21]=2[O:24][CH:25]([F:27])[F:26])[CH:5]=[O:34])[CH2:32][CH2:31]1Participants
Conditions
- Temperature
- 60 °C
Procedure
To a suspension of sodium hydride (80% dispersion in mineral oil, 11.6 g, 388 mmol) in dry 1,2-dimethoxyethane (700 mL) under an argon atmosphere was added a solution of crude dimethyl 4-cyano-4-(3-cyclopropylmethoxy-4-difluoromethoxyphenyl)pimelate (41 g) in dry 1,2-dimethoxyethane (700 mL). The resulting mixture was heated at 60° C. for 1 h, cooled to room temperature, quenched with dilute aqueous hydrochloric acid and concentrated. The residue was diluted with water, was acidified to pH 3 and was extracted twice with methylene chloride. The organic extract was washed with acidic water, was dried (sodium sulfate) and the solvent was removed in vacuo. Purification by flash chromatography, eluting with methylene chloride, followed by trituration with cold ether provided a solid (17.7 g, 43% from 3-cyclopropylmethoxy-4difluoromethoxybenzaldehyde): m.p. 115°-116° C.
Workup
- temperaturecooled to room temperature
- customquenched with dilute aqueous hydrochloric acid
- concentrationconcentrated
- additionThe residue was diluted with water
- extractionwas extracted twice with methylene chloride
- extractionThe organic extract
- washwas washed with acidic water
- dry with materialwas dried (sodium sulfate)
- customthe solvent was removed in vacuo
- customPurification by flash chromatography
- washeluting with methylene chloride
Sources & evidence
- ORD record
- ord-ffcb63804b814a68a5a46a5acc345022
- Source dataset
- uspto-grants-1995_09
- Patent number
- US05449686
Reaction notes
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