Naphthalene → 3-Cyclohexyl-4-morpholinoethoxybenzaldehyde

Temperature

-78 °C

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.

1. custom(approximately 1 hour)
2. temperaturethe reaction was warmed to 0° C.
3. stirringstirred for an additional hour
4. stirringthe reaction was stirred at 0° C. for one more hour
5. temperaturewarmed to room temperature
6. stirringstirred for another hour
7. customThe reaction was quenched with methanol (30 ml)
8. additionadded to 1N hydrochloric acid (300 ml)
9. extractionextracted with ethyl acetate (400 ml)
10. washThe organic layer was washed with water (300 ml), saturated sodium bicarbonate solution (300 ml) and brine (300 ml)
11. dry with materialdried over magnesium sulfate
12. concentrationconcentrated

ORD record

ord-755aa668e775454ba249d41e3461328d

Source dataset

uspto-grants-2005_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06855730B2