Reacción #52640

Ecuación de reacción

3-cyclohexyl-4-morpholinoethoxychlorobenzene

Naphthalene

lithium

Dimethylformamide

→

3-cyclohexyl-4-morpholinoethoxybenzaldehyde

Rendimiento 38.3%

Disolventes

tetrahydrofuran

tetrahydrofuran

tetrahydrofuran

Condiciones de reacción

Tratamiento posterior

1. 1
   Otro(approximately 1 hour)
2. 2
   Temperaturathe reaction was warmed to 0° C.
3. 3
   workup.STIRRINGstirred for an additional hour
4. 4
   workup.STIRRINGthe reaction was stirred at 0° C. for one more hour
5. 5
   Temperaturawarmed to room temperature
6. 6
   workup.STIRRINGstirred for another hour
7. 7
   OtroThe reaction was quenched with methanol (30 ml)
8. 8
   workup.ADDITIONadded to 1N hydrochloric acid (300 ml)
9. 9
   Extracciónextracted with ethyl acetate (400 ml)
10. 10
    LavadoThe organic layer was washed with water (300 ml), saturated sodium bicarbonate solution (300 ml) and brine (300 ml)
11. 11
    Secadodried over magnesium sulfate
12. 12
    Concentraciónconcentrated

Procedimiento

Naphthalene (3.48 g, 27.2 mmol) was added to a suspension of 30% lithium dispersion (3.2 g, 138 mmol, pre-washed with tetrahydrofuran) in tetrahydrofuran (80 ml). The suspension was stirred until a green color appeared (approximately 1 hour). The reaction was cooled to −78° C., and a solution of the 3-cyclohexyl-4-morpholinoethoxychlorobenzene (8 g, 24.7 mmol) in tetrahydrofuran (20 ml) was added. After 1 hour, the reaction was warmed to 0° C. and stirred for an additional hour. Dimethylformamide (9.6 ml, 123.5 mmol) was added, the reaction was stirred at 0° C. for one more hour and then warmed to room temperature and stirred for another hour. The reaction was quenched with methanol (30 ml), added to 1N hydrochloric acid (300 ml) and extracted with ethyl acetate (400 ml). The organic layer was washed with water (300 ml), saturated sodium bicarbonate solution (300 ml) and brine (300 ml), dried over magnesium sulfate and concentrated. Chromatography (silica, 40-60% ethyl acetate/hexanes) afforded 3 g (34%) of 3-cyclohexyl-4-morpholinoethoxybenzaldehyde as a light yellow oil.

Fuente