Reaktion #986272

Reaktionsgleichung

5-fluoro-2 methoxybenzyl chloride

5-fluoro-2-methoxybenzyl chloride

(4-Benzyl-morpholin-2-yl)-phenyl-methanone

Iodine crystals

5-fluoro-2-methoxybenzyl chloride

Magnesium

→

Title compound

Ausbeute 106.8%

1-(4-Benzyl-morpholin-2-yl)-2-(5-fluoro-2-methoxy-phenyl)-1-phenyl-ethanol

Ausbeute 106.8%

Lösungsmittel

diethyl ether

diethyl ether

diethyl ether

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethe reaction
2. 2
   Temperaturmaintaining the temperature of the reaction mixture below 28° C
3. 3
   workup.STIRRINGThe mixture was stirred for another 5 minutes at 19° C.
4. 4
   workup.ADDITIONafter completion of the addition
5. 5
   Sonstigea white suspension was formed
6. 6
   Temperaturmaintaining the temperature of the reaction mixture below 25° C
7. 7
   SonstigeThe suspension obtained
8. 8
   workup.STIRRINGwas stirred for 2 hours
9. 9
   SonstigeThe reaction mixture was quenched through the addition of a saturated aqueous NaHCO3 solution (625 ml) and water (500 ml)
10. 10
    Temperaturmaintaining the temperature below 20° C
11. 11
    workup.STIRRINGThe mixture was stirred for 30 minutes
12. 12
    Filtrationthe solids were filtered
13. 13
    Waschenwashed with water (125 ml) and diethyl ether (200 ml)
14. 14
    SonstigeThe filtrates were loaded into a separation funnel
15. 15
    Sonstigethe layers were separated
16. 16
    ExtraktionThe aqueous layer was extracted with diethyl ether (1 L)
17. 17
    Trocknendried over MgSO4
18. 18
    Filtrationfiltered
19. 19
    Waschenthe filter cake was washed with diethyl ether (100 ml)
20. 20
    EinengenThe filtrates were concentrated under vacuum

Vorschrift

Alternatively, the following method may be used. Magnesium turnings (21.6 g, 0.888 mole, 2 eq.) and diethyl ether (300 ml) were loaded in a reactor under N2. A solution of 5-fluoro-2-methoxybenzyl chloride (116 g, 0.664 mole, 1.5 eq.) in diethyl ether (200 ml) was loaded in an addition funnel. Iodine crystals and a small amount of the 5-fluoro-2-methoxybenzyl chloride solution were added and the reaction mixture was stirred to initiate the reaction. The remainder of the 5-fluoro-2 methoxybenzyl chloride solution was then added drop-wise maintaining the temperature of the reaction mixture below 28° C. The mixture was stirred for another 5 minutes at 19° C. after completion of the addition and a white suspension was formed. A solution of (4-Benzyl-morpholin-2-yl)-phenyl-methanone (125 g, 0.444 mole) in diethyl ether (1.8 L) was added drop-wise, maintaining the temperature of the reaction mixture below 25° C. The suspension obtained was stirred for 2 hours. The reaction mixture was quenched through the addition of a saturated aqueous NaHCO3 solution (625 ml) and water (500 ml), maintaining the temperature below 20° C. The mixture was stirred for 30 minutes and the solids were filtered, washed with water (125 ml) and diethyl ether (200 ml). The filtrates were loaded into a separation funnel and the layers were separated. The aqueous layer was extracted with diethyl ether (1 L). The organic layers were combined and dried over MgSO4, filtered and the filter cake was washed with diethyl ether (100 ml). The filtrates were concentrated under vacuum. The yield of title compound was 201 g as a yellow solid (107%). Title compound (200 g, 0.474 mole) was then suspended in isopropanol (400 ml) under N2. The suspension was heated under reflux until all solids were dissolved. The solution is allowed to cool to 20° C. over 4 hours under stirring. The solid is filtered, washed with isopropanol (100 ml) and dried at 40° C. under vacuum. The yield of pure title compound is 158 g (79%). 1H-NMR (CDCl3): 6.99-7.26 ppm, 10H, mp; 6.60-6.71 ppm, 1H, dt; 6.49-6.60 ppm, 1H, dd; 6.31-6.44 ppm, 1H, dd; 3.92-4.01 ppm, 1H, dt; 3.80-3.90 ppm, 1H, dd; 3.64-3.73 ppm, 1H, dd; 3.59-3.64 ppm, 1H, d; 3.52-3.59 ppm, 3+1 H, 2s; 3.37-3.45 ppm, 1H, d; 3.07-3.17 ppm, 1H, d; 2.84-2.92 ppm, 1H, d; 2.43-2.53 ppm, 1H, d; 2.20-2.28 ppm, 1H, d; 1.98-2.11 ppm, 2H, mp.

Quelle