تفاعل #44650

معادلة التفاعل

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

hydrochloric acid ethyl acetate

→

titled compound

المردود 51.1%

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

المردود 51.1%

المذيبات

ethyl acetate

ظروف التفاعل

المعالجة

1. 1
   أخرىSolvent 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
   ترشيحThe 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
   ترشيحThe catalyst was filtered off over Celite, and solvent
7. 7
   أخرىwas removed by distillation under reduced pressure
8. 8
   غسيلThe residue was passed through a silica pad (carrier: silica gel, 500 cc; elution solvent: 5% triethylamine/ethyl acetate, 6 L)
9. 9
   تركيزthe filtrate was then concentrated by distillation under reduced pressure
10. 10
    workup.ADDITIONThe residue was diluted with ethyl acetate
11. 11
    غسيلThe resultant solution was washed with brine
12. 12
    تجفيفdried over anhydrous magnesium sulfate
13. 13
    أخرىSolvent was removed by distillation under reduced pressure

الإجراء التجريبي

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).

المصدر