반응 #44650

반응 방정식

{(1R,2R)-2-benzyloxy-1-[2-oxo-2-(3,4,5trifluorophenyl)ethoxymethyl]-propyl}carbamic acid t-butyl ester

hydrochloric acid ethyl acetate

→

titled compound

수율 51.1%

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

수율 51.1%

용매

ethyl acetate

반응 조건

후처리

1. 1
   기타Solvent was removed by distillation under reduced pressure
2. 2
   workup.ADDITIONto the resultant product in methanol (100 ml) was added 10% palladium-carbon (1 g, 50% water content)
3. 3
   여과The catalyst was filtered off over Celite
4. 4
   workup.ADDITIONTo the resultant product was added methanol (100 ml) and 20% palladium hydroxide-carbon (1 g)
5. 5
   workup.STIRRINGunder a hydrogen atmosphere, the reaction mixture was stirred for 8 hours
6. 6
   여과The catalyst was filtered off over Celite, and solvent
7. 7
   기타was removed by distillation under reduced pressure
8. 8
   세척The residue was passed through a silica pad (carrier: silica gel, 500 cc; elution solvent: 5% triethylamine/ethyl acetate, 6 L)
9. 9
   농축the filtrate was then concentrated by distillation under reduced pressure
10. 10
    workup.ADDITIONThe residue was diluted with ethyl acetate
11. 11
    세척The resultant solution was washed with brine
12. 12
    건조dried over anhydrous magnesium sulfate
13. 13
    기타Solvent was removed by distillation under reduced pressure

실험 절차

To a solution of {(1R,2R)-2-benzyloxy-1-[2-oxo-2-(3,4,5trifluorophenyl)ethoxymethyl]-propyl}carbamic acid t-butyl ester (13.9 g, purity: about 84.9%) in ethyl acetate (20 mL) was added a 4 N hydrochloric acid/ethyl acetate solution (63 mL), and the resultant solution was stirred at room temperature for 5 hours. Solvent was removed by distillation under reduced pressure, and to the resultant product in methanol (100 ml) was added 10% palladium-carbon (1 g, 50% water content). Under a hydrogen atmosphere, the reaction mixture was stirred for 10 hours. The catalyst was filtered off over Celite. To the resultant product was added methanol (100 ml) and 20% palladium hydroxide-carbon (1 g), and under a hydrogen atmosphere, the reaction mixture was stirred for 8 hours. The catalyst was filtered off over Celite, and solvent was removed by distillation under reduced pressure. The residue was passed through a silica pad (carrier: silica gel, 500 cc; elution solvent: 5% triethylamine/ethyl acetate, 6 L), and the filtrate was then concentrated by distillation under reduced pressure. The residue was diluted with ethyl acetate. The resultant solution was washed with brine, and then dried over anhydrous magnesium sulfate. Solvent was removed by distillation under reduced pressure, to thereby obtain the titled compound (3.97 g). The physical properties of the compound were as follows. ESI-MS; m/z 262 [M++H]. 1H-NMR (CDCl3) δ (ppm): 1.22 (d, J=6.8 Hz, 3H), 1.93 (brs, 1H), 2.88 (ddd, J=10.0, 6.8, 3.6 Hz, 1H), 3.14 (dd, J=11.2, 10.0 Hz, 1H), 3.31 (dd, J=10.4, 10.4 Hz, 1H), 3.64 (ddd, J=12.4, 6.0, 6.0 Hz, 1H), 3.76 (dd, J=11.2, 3.2 Hz, 1H), 3.83 (dd, J=11.2, 3.2 Hz, 1H), 3.91 (dd, J=10.0, 3.2 Hz, 1H), 7.05 (dd, J=8.0, 6.4 Hz, 2H).

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