A dry,
2-L, three-necked, round-bottomed flask is equipped with a
magnetic stirrer and
two 500-mL pressure-equalizing dropping funnels. One of the dropping funnels is fitted with a
rubber septum and the air in the system is replaced with dry
nitrogen (Note
1). The flask is charged with
400 mL of anhydrous tetrahydrofuran (Note
2) and
51.6 g (71.5 mL, 0.51 mol) of anhydrous diisopropylamine (Note
3). The flask is cooled to 0°C with an
ice bath. A
1.7 M hexane solution of
butyllithium (288 mL, 0.49 mol) is added dropwise with stirring over a 30-min period. The resulting
lithium diisopropylamide is cooled to −78°C with a
dry ice–acetone bath (Note
4). A solution of
53.9 g (0.385 mol) of 3-ethoxy-2-cyclohexen-1-one (Note
5) in
250 mL of anhydrous tetrahydrofuran is added dropwise with stirring at −78°C over a 1-hr period. The solution is stirred at −78°C for 30 min followed by the rapid addition of
114 g (50 mL, 0.80 mol) of methyl iodide (Note
6). After 5 min, the cooling bath is removed and the mixture is allowed to warm to room temperature and is stirred overnight. The reaction is quenched with 300 mL of water and the organic phase is separated. The aqueous phase is extracted four times with
75 mL of diethyl ether. The organic phases are combined and washed twice with 150 mL of water, once with
150 mL of brine, and dried over
magnesium sulfate. Solvent removal on a
rotary evaporator followed by distillation at reduced pressure affords
54–55 g (
91–93%) of
3-ethoxy-6-methyl-2-cyclohexen-1-one as a colorless oil, bp
131–133°C (15 mm) (Note
7) and (Note
8).