反应详情

温度

-10 °C

To a solution of 4-benzyl-morpholine-2-carbonitrile (10 g, 49.5 mmol) in dry diethyl ether (100 mL) at −10° C. under an atmosphere of nitrogen is added a solution of 2-methoxybenzylmagnesium chloride (0.25M solution in tetrahydrofuran, 218 mL, 54.5 mmol) available from Aldrich Chemical Company or Rieke Metals) and the reaction mixture is further stirred at −10° C. for 30 minutes. Then the reaction is allowed to warm to room temperature and stirred overnight The reaction is then cooled to 0° C. and quenched by addition of hydrochloric acid (5N aqueous solution, 50 mL) and the resulting mixture is stirred for 10 minutes at 0° C. Next the solution is basified with sodium hydroxide (2N aqueous solution), filtered through Celite® then extracted with diethyl ether, the organics collected, dried (MgSO4) and the solvent removed under reduced pressure to give a residue which is taken up into methanol and purified by SCX-2 chromatography prior to silica gel chromatography (eluent, ethyl acetate/n-hexane, 0/100 to 40/60 [v/v]). The fractions containing the correct mass (FIA+[M+H]+=447) are collected and purified via preparative HPLC to give 80 (72 mg). MW 566.69; C28H34N2O3.C4H8O4; LCMS (12 minutes method): m/z)=447.2 [M−C4H8O4+H]+ RT 4.60 min.

1. temperatureto warm to room temperature
2. stirringstirred overnight The reaction
3. temperatureis then cooled to 0° C.
4. customquenched by addition of hydrochloric acid (5N aqueous solution, 50 mL)
5. stirringthe resulting mixture is stirred for 10 minutes at 0° C
6. filtrationfiltered through Celite®
7. extractionthen extracted with diethyl ether
8. dry with materialthe organics collected, dried (MgSO4)
9. customthe solvent removed under reduced pressure
10. customto give a residue which
11. custompurified by SCX-2 chromatography
12. additionThe fractions containing the correct mass (FIA+[M+H]+=447)
13. customare collected
14. custompurified via preparative HPLC