Reaktion #439564

Reaktionsgleichung

sodium 3-aminobenzoate

(R)-(−)-1-tert-butylcarbonylmethyl-2-oxo-3-phenoxycarbonylamino-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine

→

title compound

Ausbeute 70.9%

(R)-(−)-3-[3-(1-tert-butylcarbonylmethyl-2-oxo-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepin-3-yl)ureido]benzoic acid

Ausbeute 70.9%

Lösungsmittel

dimethylsulfoxide

Reaktionsbedingungen

Aufarbeitung

1. 1
   FiltrationAfter filtration of the reaction mixture, ice water
2. 2
   workup.ADDITIONa 1N aqueous solution of sodium hydroxide were added to the filtrate
3. 3
   ExtraktionThe mixture was extracted with ethyl acetate
4. 4
   WaschenThe organic layer was washed successively with a 1N aqueous solution of sodium hydroxide, 1N hydrochloric acid and brine
5. 5
   Trocknendried over anhydrous sodium sulfate
6. 6
   Sonstigeevaporated under reduced pressure
7. 7
   workup.ADDITIONTo the residue was added a mixed solvent of ethanol and water (2:1)
8. 8
   SonstigeCrystals so precipitated
9. 9
   Filtrationwere collected by filtration

Vorschrift

Under an argon atmosphere, 2.0 g of sodium 3-aminobenzoate, 77 mg of 4-dimethylaminopyridine and 3.0 g of Molecular Sieves 3A were added to a solution of 3.0 g of (R)-(−)-1-tert-butylcarbonylmethyl-2-oxo-3-phenoxycarbonylamino-5-cyclohexyl-1,3,4,5-tetrahydro-2H-1,5-benzodiazepine in 30 ml of anhydrous dimethylsulfoxide. The mixture was stirred at room temperature for 15 hours. After filtration of the reaction mixture, ice water and a 1N aqueous solution of sodium hydroxide were added to the filtrate. The mixture was extracted with ethyl acetate. The organic layer was washed successively with a 1N aqueous solution of sodium hydroxide, 1N hydrochloric acid and brine, dried over anhydrous sodium sulfate and evaporated under reduced pressure. To the residue was added a mixed solvent of ethanol and water (2:1). Crystals so precipitated were collected by filtration, whereby 2.32 g of the title compound was obtained.

Quelle