Reaktion #986268

Reaktionsgleichung

1-(4-Benzyl-morpholin-2-yl)-1-phenyl-2-(2-trifluoromethoxy-phenyl)-ethanol hydrochloride

water

→

title compound

Ausbeute 81.0%

(S,R) 1-Morpholin-2-yl-1-phenyl-2-(2-trifluoromethoxy-phenyl)-ethanol hydrochloride

Ausbeute 81.0%

Lösungsmittel

i-PrOH

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeThe heterogeneous reaction mixture was then purged 5 times with 25 psi nitrogen
2. 2
   Sonstigethen purged 5 times with 50 psi hydrogen
3. 3
   Sonstigewas performed at RT
4. 4
   Sonstigewas 22° C.
5. 5
   Sonstigewas 23° C
6. 6
   workup.WAITThe hydrogenation was stopped after 3 hours
7. 7
   SonstigeThe nitrogen purged
8. 8
   Sonstigereaction mixture
9. 9
   Filtrationwas then filtered at RT through an hyflo
10. 10
    Filtrationfilter (56 g)
11. 11
    Waschenwashed with 300 mL of a 50/50 v/v isopropanol/water mixture
12. 12
    workup.WAITThe filtrates were stored overnight at RT
13. 13
    EinengenThe filtrates were concentrated at 40-50° C. under reduced pressure (typical 622 g distilled)
14. 14
    workup.STIRRINGpost-agitated
15. 15
    workup.WAITAfter 3 hours
16. 16
    Temperaturcooled to 0° C.
17. 17
    Sonstigecrystallization
18. 18
    workup.ADDITIONThese seeds were added to the reaction mixture and precipitation
19. 19
    workup.WAITwas observed within a few minutes
20. 20
    workup.STIRRINGThe mixture was post-agitated at RT for 2 hours
21. 21
    FiltrationThe crystals were filtered
22. 22
    Waschenrinsed with H20 (30 mL)
23. 23
    SonstigeThen, the precipitate was dried under reduced pressure (400 mmHg) with a nitrogen flow (0.1 bar) for 4 hours

Vorschrift

Alternatively, the following method may be used. In a glass-lined nitrogen purged hydrogenator are charged 1-(4-Benzyl-morpholin-2-yl)-1-phenyl-2-(2-trifluoromethoxy-phenyl)-ethanol hydrochloride (150 g, 303.7 mmol), demineralized water (352 mL), i-PrOH (375 mL) and 5% Pd/C (30 g, 50% water, Johnson & Matthey type 440). The heterogeneous reaction mixture was then purged 5 times with 25 psi nitrogen then purged 5 times with 50 psi hydrogen, and the hydrogenation was performed at RT. The initial Tmass was 22° C. and the maximum Tmass during the hydrogenation was 23° C. The reactor was stirred vigorously. In-process analysis after 2 hours indicated complete hydrogenolysis. The hydrogenation was stopped after 3 hours. The nitrogen purged reaction mixture was then filtered at RT through an hyflo filter (56 g), impregnated beforehand with 75 mL of a 50/50 v/v isopropanol/water mixture and washed with 300 mL of a 50/50 v/v isopropanol/water mixture. The filtrates were stored overnight at RT. The filtrates were concentrated at 40-50° C. under reduced pressure (typical 622 g distilled). The reaction mixture was cooled to RT and post-agitated. After 3 hours, 1 mL of the solution was taken and cooled to 0° C. to initiate crystallization. These seeds were added to the reaction mixture and precipitation was observed within a few minutes. The mixture was post-agitated at RT for 2 hours. The crystals were filtered and rinsed with H20 (30 mL). Then, the precipitate was dried under reduced pressure (400 mmHg) with a nitrogen flow (0.1 bar) for 4 hours affording the title compound as the hydrate polymorph (103.5 g, 81% yield).

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