Tetrahydrofuran → N-[(2,2-Dimethoxy)ethyl]-N-(2-pyridyl)cyclohexanecarboxamide
Reaction equation
[CH3:1][O:2][CH:3]([O:12][CH3:13])[CH2:4][NH:5][C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][N:7]=1.[CH2:14]([Li])[CH2:15][CH2:16]C.[O:19]1[CH2:23][CH2:22][CH2:21][CH2:20]1>>[CH3:1][O:2][CH:3]([O:12][CH3:13])[CH2:4][N:5]([C:6]1[CH:11]=[CH:10][CH:9]=[CH:8][N:7]=1)[C:23]([CH:22]1[CH2:16][CH2:15][CH2:14][CH2:20][CH2:21]1)=[O:19]Participants
4
Conditions
- Temperature
- 0 °C
Procedure
To a solution comprising 5.97 g 2-(2,2-dimethoxyethylamino)pyridine (prepared as described by I. Kaye, in J. Am. Chem. Soc., 73, 5467 (195 1)) in 40 mL tetrahydrofurane, stirred under a nitrogen atmosphere at 0° C., was added, in a dropwise manner, 13.1 mL butyl lithium (2.5 M, in hexane). This was followed by removal of the cooling bath, and stirring of the obtained mixture for 1 h, at room temperature. There was then added, in a dropwise manner, 4.46 mL cyclohexanecarbonyl chloride. Then, after 5.5 h stirring at room temperature, 2 mL methanol was added. The solution was then evaporated to dryness under a vacuum, yielding a chestnut-colored oil; this product was then purified by flash chromatography (chloroform—ethyl acetate 7:3). The fractions containing the product were evaporated to dryness affording 8.3 g of Compound 1A (yield 78%); this substance was suitable for use in subsequent reactions with no additional purification processing.