반응 #48693

반응 방정식

sodium bicarbonate

(3S,5R)-5-[(1S,2S)-1-benzyloxy-2-dibenzylamino-3-(3,5-difluorophenyl)-propyl]-3-methylmorpholin-2-ol

neopentanol

methanesulphonic acid

→

desired compound

수율 56.0%

Dibenzyl-{(1S,2S)-2-benzyloxy-1-(3,5-difluorobenzyl)-2-[(3R,5S,6R)-6-(2,2-dimethylpropoxy)-5-methylmorpholin-3-yl]-ethyl}-amine

수율 56.0%

용매

dichloromethane

dichloromethane

반응 조건

후처리

1. 1
   workup.ADDITIONAdd 4 Å molecular sieves (850 mg)
2. 2
   추출Extract the aqueous layer with dichloromethane
3. 3
   건조dry (sodium sulfate)
4. 4
   여과filter
5. 5
   농축concentrate
6. 6
   기타purify
7. 7
   세척(silica gel chromatography, eluting with 100:0 to 90:10 hexanes:ethyl acetate)

실험 절차

Mix (3S,5R)-5-[(1S,2S)-1-benzyloxy-2-dibenzylamino-3-(3,5-difluorophenyl)-propyl]-3-methylmorpholin-2-ol (1.06 g, 1.85 mmol) with neopentanol (1.63 g, 18.5 mmol,) in dichloromethane (0.2 mL). Add 4 Å molecular sieves (850 mg), then methanesulphonic acid (2.4 mL, 37 mmol) and heat at 50° C. for 4 hours. Cool to room temperature, dilute with dichloromethane and add slowly to a solution of saturated aqueous sodium bicarbonate. Extract the aqueous layer with dichloromethane, dry (sodium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 100:0 to 90:10 hexanes:ethyl acetate) to give the desired compound as a white solid (665 mg, 56% yield).

출처