Reaktion #41395

Reaktionsgleichung

1-{[6-Chloro-1-(4-fluorophenyl)-1H-indazol-5-yl]oxy}-1-(4-fluorophenyl)acetone

ammonium acetate

cyanoborohydride

→

(1RS,2RS)-1-[6-chloro-1-(4-fluorophenyl)indazol-5-yl]oxy-1-(4-fluorophenyl)propan-2-amine

Lösungsmittel

methanol

Reaktionsbedingungen

Aufarbeitung

1. 1
   EinengenThe mixture was concentrated
2. 2
   workup.ADDITIONtreated with NaHCO3 and DCM
3. 3
   EinengenThe organic phase was concentrated
4. 4
   Sonstigethe crude product was purified by flash chromatography (EtOAc/heptane followed by EtOAc/methanol)
5. 5
   SonstigeThe diasteromers were separated on preparative HPLC (Kromasil column, water

Vorschrift

1-{[6-Chloro-1-(4-fluorophenyl)-1H-indazol-5-yl]oxy}-1-(4-fluorophenyl)acetone (500 mg, 1.21 mmol), ammonium acetate (934 mg, 12.11) and cyanoborohydride on polymer support (1.82 g, 3.63 mmol) were mixed in methanol (3 ml) and heated in micro at 140° C. for 10 min. The mixture was concentrated and treated with NaHCO3 and DCM. The organic phase was concentrated and the crude product was purified by flash chromatography (EtOAc/heptane followed by EtOAc/methanol). The diasteromers were separated on preparative HPLC (Kromasil column, water buffered with 2 g NH4OAc/l, pH set to 5.5 with HOAc, and MeCN, 25%-75%) to give the syn-isomer (1RS,2RS)-1-[6-chloro-1-(4-fluorophenyl)indazol-5-yl]oxy-1-(4-fluorophenyl)propan-2-amine (98a-rac-1) as first eluated isomer (assignment by 1H-NMR).

Quelle