Reaktion #157073

Reaktionsgleichung

(+/−) benzyl 3-amino-4-hydroxypiperidine-1-carboxylate

(+/−) benzyl 4-amino-3-hydroxypiperidine-1-carboxylate

Boc2O

triethylamine

(+/−) benzyl 7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylate

→

(+/−)-benzyl 3-(tert-butoxycarbonylamino)-4-hydroxypiperidine-1-carboxylate

(+/−)-benzyl 4-(tert-butoxycarbonylamino)-3-hydroxypiperidine-1-carboxylate

Lösungsmittel

dichloromethane

ammonium hydroxide

ethanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   SonstigeAfter all volatile materials were removed by N2 gas stream, ethyl acetate and water
2. 2
   workup.ADDITIONwere added for work-up
3. 3
   Extraktionthe reaction mixture was extracted with dichloromethane

Vorschrift

A solution of (+/−) benzyl 7-oxa-3-azabicyclo[4.1.0]heptane-3-carboxylate (1.0 equiv.) in saturated ammonium hydroxide aqueous solution and ethanol (1:1, 0.05 M solution) in a sealed steel bomb was heated to 70° C. for 5 h. After all volatile materials were removed by N2 gas stream, ethyl acetate and water were added for work-up. The crude regioisomeric mixture, (+/−) benzyl 3-amino-4-hydroxypiperidine-1-carboxylate and (+/−) benzyl 4-amino-3-hydroxypiperidine-1-carboxylate was reacted with Boc2O (1.0 equiv.) and triethylamine (1.0 equiv.) in dichloromethane (0.1 M solution). After stirred for 2 h at room temperature, the reaction mixture was extracted with dichloromethane. The polar (+/−)-benzyl 3-(tert-butoxycarbonylamino)-4-hydroxypiperidine-1-carboxylate and nonpolar (+/−)-benzyl 4-(tert-butoxycarbonylamino)-3-hydroxypiperidine-1-carboxylate were obtained by flash column chromatography (20% to 40% EtOAc in hexanes, 28% and 51% each). LCMS (m/z): 351.1 (MH+), Rt=0.81 min, LCMS (m/z): 351.1 (MH+), Rt=0.83 min.

Quelle