Reaktion #82280

Reaktionsgleichung

hydrochloric acid

ethyl (+)-3-(7-amidino-2-naphthyl)-2-[4-[((3S)-3-pyrrolidinyl)oxy]phenyl]propionate dihydrochloride

ethyl acetimidate hydrochloride

triethylamine

→

title compound

Ausbeute 193.4%

ethyl (+)-2-[4-[((3S)-1-acetimidoyl-3-pyrrolidinyl)oxy]phenyl]-3-(7-amidino-2-naphthyl)propionate dihydrochloride

Ausbeute 193.4%

Lösungsmittel

ethanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   workup.STIRRINGWith ice cooling and stirring
2. 2
   Sonstigeat 3° to 5° C.
3. 3
   Sonstigeat 5° C. or below
4. 4
   workup.DISTILLATIONAfter distilling off the solvent under a reduced pressure at a low temperature
5. 5
   Sonstigethe resulting reaction solution
6. 6
   workup.DISTILLATIONfollowed by further distillation under a reduced pressure
7. 7
   Sonstigeto remove the solvent
8. 8
   SonstigeThe resulting residue was purified
9. 9
   workup.ADDITIONmixed with a small amount of dilute hydrochloric acid
10. 10
    Einengenconcentrated to dryness

Vorschrift

In 1,000 ml of ethanol was dissolved 105.3 g of ethyl (+)-3-(7-amidino-2-naphthyl)-2-[4-[((3S)-3-pyrrolidinyl)oxy]phenyl]propionate dihydrochloride. With stirring at room temperature, the thus prepared solution was mixed with 51.5 g of ethyl acetimidate hydrochloride. With ice cooling and stirring, 89 ml of triethylamine was added dropwise to the above solution while keeping the inner temperature at 3° to 5° C., and the stirring was continued for 2.5 hours while keeping the temperature at 5° C. or below. After distilling off the solvent under a reduced pressure at a low temperature, the resulting reaction solution was adjusted to pH 4-5 with dilute hydrochloric acid, followed by further distillation under a reduced pressure to remove the solvent. The resulting residue was purified by subjecting it to column chromatography using a column packed with a highly porous polymer type synthetic adsorbent (styrene-divinylbenzene polymer: Diaion HP-20) and using a water/acetonitrile mixture as an elution solvent. Thereafter, thus eluted fractions of interest were pooled, mixed with a small amount of dilute hydrochloric acid, and then concentrated to dryness. In this way, 110.1 g of the title compound was obtained in the form of a colorless solid.

Quelle