반응 #44651

반응 방정식

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

triphenylphosphine

4-nitrobenzoic acid

diisopropyl azodicarboxylate

sodium methoxide

→

titled compound

수율 52.9%

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

수율 52.9%

용매

tetrahydrofuran

methanol

water

ethyl acetate

반응 조건

후처리

1. 1
   온도while cooling with ice
2. 2
   기타the organic layer was partitioned
3. 3
   세척The organic layer was washed with brine
4. 4
   건조dried over anhydrous magnesium sulfate
5. 5
   기타Solvent was removed by distillation under reduced pressure
6. 6
   기타the resulting residue was crudely purified by silica gel column chromatography (heptane/ethyl acetate 8/2→1/1)
7. 7
   기타to 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
   기타Solvent was removed by distillation under reduced pressure
9. 9
   workup.ADDITIONthe resultant product was diluted with ethyl acetate and water
10. 10
    기타The organic layer was partitioned
11. 11
    세척washed with brine
12. 12
    건조dried over anhydrous magnesium sulfate
13. 13
    기타Solvent was removed by distillation under reduced pressure
14. 14
    기타the resulting residue was purified by silica gel column chromatography (heptane/ethyl acetate 9/1→1/1)

실험 절차

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.

출처