Réaction #48708

Équation de réaction

trimethylsilyl trifluoromethanesulfonate

potassium carbonate

(1-fluorocyclohexyl)-methanol

trimethylsilyl trifluoromethanesulfonate

triphosgene

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

triethylamine

→

title compound

Rendement 31.2%

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

Rendement 31.2%

Solvants

dichloromethane

Conditions de réaction

Traitement

1. 1
   workup.STIRRINGStir at 0° C. for 1 hour and at room temperature for 2 hours
2. 2
   workup.STIRRINGstir at room temperature for 30 min
3. 3
   Autreseparate the organic layer
4. 4
   Extractionextract the aqueous layer with dichloromethane
5. 5
   Séchagedry (sodium sulfate)
6. 6
   Filtrationfilter
7. 7
   Concentrationconcentrate
8. 8
   Autrepurify
9. 9
   Lavage(silica gel chromatography, eluting with 0:100 to 20:80 hexanes:ethyl acetate)

Mode opératoire

Add triphosgene (246 mg, 0.79 mmol) at room temperature to a solution of (3S,5R)-5-[(1R,2S)-1-benzyloxy-2-dibenzylamino-3-(3,5-difluorophenyl)-propyl]-3-methylmorpholin-2-ol (1 g, 1.75 mmol) and triethylamine (0.99 mL, 7 mmol) in anhydrous dichloromethane (17 mL). Stir for 30 min, cool to 0° C. and add (1-fluorocyclohexyl)-methanol (1.16 g, 8.75 mmol) and trimethylsilyl trifluoromethanesulfonate (TMSOTf) (0.64 mL, 3.5 mmol). Stir at 0° C. for 1 hour and at room temperature for 2 hours. Add more trimethylsilyl trifluoromethanesulfonate (0.16 mL, 0.87 mmol) and stir at room temperature for 30 min. Add 10% aqueous potassium carbonate, separate the organic layer and extract the aqueous layer with dichloromethane. Combine the organic layers, dry (sodium sulfate), filter, concentrate and purify (silica gel chromatography, eluting with 0:100 to 20:80 hexanes:ethyl acetate), to give the title compound as a colorless oil (375 mg).

Source