Reaktion #986266

Reaktionsgleichung

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

ACE-Cl

→

title compound

Ausbeute 33.0%

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

Ausbeute 33.0%

Lösungsmittel

1,2-dichloroethane

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.WAITThe reaction mixture was left
2. 2
   SonstigeAll volatiles were evaporated under vacuum
3. 3
   FiltrationThe solution was filtered through acid ion exchange column
4. 4
   Sonstigethe required fractions evaporated to dryness
5. 5
   Filtrationthe insoluble material filtered off
6. 6
   EinengenThe mother liquor was concentrated in vacuo
7. 7
   Sonstigepurified via preparative HPLC
8. 8
   workup.ADDITIONBoth fractions were mixed (from slurry and from HPLC)
9. 9
   workup.ADDITIONHydrogen chloride was added (large excess of 2M solution in diethyl ether)
10. 10
    workup.STIRRINGthe mixture stirred
11. 11
    SonstigeThen all the volatiles were evaporated in vacuo

Vorschrift

To a solution of 1-(4-Benzyl-morpholin-2-yl)-1-phenyl-2-(2-trifluoromethoxy-phenyl)-ethanol (7 g, 1 equiv.) in dry 1,2-dichloroethane (40 mL) at 0° C. under nitrogen atmosphere was added ACE-Cl (20.33 g, 10 equiv.). The reaction mixture was left to warm to room temperature for 48 hours. All volatiles were evaporated under vacuum, and the resulting solid was taken-up with methanol (50 mL) and stirred at room temperature overnight. The solution was filtered through acid ion exchange column and the required fractions evaporated to dryness. The resulting solid was taken up with acetonitrile and the insoluble material filtered off. The mother liquor was concentrated in vacuo and purified via preparative HPLC. Both fractions were mixed (from slurry and from HPLC) and taken up in ethanol. Hydrogen chloride was added (large excess of 2M solution in diethyl ether) and the mixture stirred. Then all the volatiles were evaporated in vacuo, to give 1.9 g of the title compound as a white solid (33%). 1H NMR (300 MHz, DMSO D6) δ: 2.45-2.50 (m, 1H), 2.81-2.97 (m, 2H), 3.18-3.30 (m, 3H), 3.89-3.97 (m, 1H), 4.15-4.18 (m, 2H), 7.02-7.29 (m, 9H), 9.18 (bs, 2H). LCMS (12 minutes method) [M+H]+=368 @ Rt 4.88 min. single major peak. NET Ki=12.39 nM.

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