Reaktion #44651

Reaktionsgleichung

(R)-1-[(3R,5R)-5-(3,4,5-trifluorophenyl)morpholine-3-yl]ethanol

triphenylphosphine

4-nitrobenzoic acid

diisopropyl azodicarboxylate

sodium methoxide

→

titled compound

Ausbeute 52.9%

(S)-1-[(3R,5R)-5-(3,4,5-trifluorophenyl)morpholine-3-yl]ethanol

Ausbeute 52.9%

Lösungsmittel

tetrahydrofuran

methanol

water

ethyl acetate

Reaktionsbedingungen

Aufarbeitung

1. 1
   Temperaturwhile cooling with ice
2. 2
   Sonstigethe organic layer was partitioned
3. 3
   WaschenThe organic layer was washed with brine
4. 4
   Trocknendried over anhydrous magnesium sulfate
5. 5
   SonstigeSolvent was removed by distillation under reduced pressure
6. 6
   Sonstigethe resulting residue was crudely purified by silica gel column chromatography (heptane/ethyl acetate 8/2→1/1)
7. 7
   Sonstigeto thereby obtain a crude product (3.6 g) of 4-nitrobenzoic acid (S)-1-[(3R,5R)-5-(3,4,5-trifluorophenyl)morpholine-3-yl]ethyl ester
8. 8
   SonstigeSolvent was removed by distillation under reduced pressure
9. 9
   workup.ADDITIONthe resultant product was diluted with ethyl acetate and water
10. 10
    SonstigeThe organic layer was partitioned
11. 11
    Waschenwashed with brine
12. 12
    Trocknendried over anhydrous magnesium sulfate
13. 13
    SonstigeSolvent was removed by distillation under reduced pressure
14. 14
    Sonstigethe resulting residue was purified by silica gel column chromatography (heptane/ethyl acetate 9/1→1/1)

Vorschrift

Under a nitrogen atmosphere, to a tetrahydrofuran (50 mL) solution containing (R)-1-[(3R,5R)-5-(3,4,5-trifluorophenyl)morpholine-3-yl]ethanol (2.25 g), triphenylphosphine (4.51 g) and 4-nitrobenzoic acid (2.88 g) was dropwise added diisopropyl azodicarboxylate (3.39 mL) while cooling with ice. The resultant solution was stirred at the same temperature for 30 minutes, and then at room temperature for 2 hours. The reaction solution was diluted with water and ethyl acetate, and the organic layer was partitioned. The organic layer was washed with brine, and then dried over anhydrous magnesium sulfate. Solvent was removed by distillation under reduced pressure, and the resulting residue was crudely purified by silica gel column chromatography (heptane/ethyl acetate 8/2→1/1), to thereby obtain a crude product (3.6 g) of 4-nitrobenzoic acid (S)-1-[(3R,5R)-5-(3,4,5-trifluorophenyl)morpholine-3-yl]ethyl ester. A solution of the obtained crude product (3.53 g) in methanol (300 mL) was added sodium methoxide (4.39 mL, 28% methanol solution), and the resultant solution was stirred at room temperature for 1 hour. Solvent was removed by distillation under reduced pressure, and the resultant product was diluted with ethyl acetate and water. The organic layer was partitioned, washed with brine, and then dried over anhydrous magnesium sulfate. Solvent was removed by distillation under reduced pressure, and the resulting residue was purified by silica gel column chromatography (heptane/ethyl acetate 9/1→1/1), to thereby obtain the titled compound (1.19 g). The physical properties of the compound were as follows.

Quelle