反应详情

温度

8 °C

Solid magnesium turnings (4.6 g, 48 equiv.) under nitrogen atmosphere at room temperature were stirred vigorously with a magnetic stirring bar overnight. The magnesium was then covered with dry tetrahydrofuran. A cold bath was then applied followed by dropwise addition of 1-chloromethyl-2-isopropoxy-benzene (3.0 g, 4 equiv. prepared as described above) in tetrahydrofuran (40 mL). During slow addition of the electrophile no exotherm was observed so on completion of addition 3 crystals of Iodine were added to promote initiation of the reaction. After this addition the reaction temperature was allowed to spike to 50° C. then cooled rapidly to 8° C. before being left to warm to room temperature for one hour. The resulting black suspension was cooled down to −10° C. and a solution of (4-Benzyl-morpholin-2-yl)-phenyl-methanone (1.2 g, 1 equiv.) in tetrahydrofuran (10 mL) was then added dropwise. The reaction mixture was left to warm to room temperature over thirty minutes and then quenched by addition of aqueous saturated solution of NaHCO3 (50 mL) prior to filtration through Celite. The aqueous solution was extracted with diethyl ether, the organic phase dried with MgSO4, evaporated in vacuo to give 3 g of a yellow amorphous solid. The compound was taken without further purification in the next step. LCMS (6 minutes method) [M+H]+=432 @ Rt 3.25 min. major peak.

1. additionDuring slow addition of the electrophile no exotherm
2. additionwere added
3. custominitiation of the reaction
4. additionAfter this addition the reaction temperature
5. customto spike to 50° C.
6. waitbefore being left
7. temperatureto warm to room temperature for one hour
8. temperatureThe resulting black suspension was cooled down to −10° C.
9. waitThe reaction mixture was left
10. temperatureto warm to room temperature over thirty minutes
11. customquenched by addition of aqueous saturated solution of NaHCO3 (50 mL)
12. filtrationto filtration through Celite
13. extractionThe aqueous solution was extracted with diethyl ether
14. dry with materialthe organic phase dried with MgSO4
15. customevaporated in vacuo