反应详情

温度

-13 °C

4-(6-Methyl-pyridin-3-ylmethyl)-morpholine (20 g, 104 mmol) and diethylcarbonate (12.4 g, 104 mmol) were dissolved in tetrahydrofuran (100 ml) under an inert atmosphere. The solution was cooled to −13° C. and lithium diisopropylamide solution (144 ml, 1.8M, 259 mmol) added dropwise over 2 hr 45 min. After stirring for an additional 30 min the reaction mixture was added to a cold aqueous solution of ammonium chloride (68.2 ml, 4.58M, 312.1 mmol) at 0° C. The biphasic mixture was warm to 30° C. and separated. The aqueous layer was extracted twice with tetrahydrofuran (80 ml) and the combined organic layers were concentrated under vacuum to give (5-Morpholin-4-ylmethyl-pyridin-2-yl)-acetic acid ethyl ester (27.20 g, 80% yield (based on 80.7 w/w % assay). (The crude product mixture is used in example 8). Characterisation data were in accordance with example 5.

1. temperatureThe biphasic mixture was warm to 30° C.
2. customseparated
3. extractionThe aqueous layer was extracted twice with tetrahydrofuran (80 ml)
4. concentrationthe combined organic layers were concentrated under vacuum