Reaktion #158455

Reaktionsgleichung

tetra-n-butylammonium fluoride

THF

BOP-Cl

tert-butyl 3-hydroxy-3-(4-(N′-hydroxycarbamimidoyl)phenyl)azetidine-1-carboxylate

Intermediate 4

tert-butyl 3-hydroxy-3-(4-(N′-hydroxycarbamimidoyl)phenyl)azetidine-1-carboxylate

3-(1-(3,5-dichlorophenyl)cyclohexyl)propanoic acid

diisopropylethyl amine

→

tert-butyl 3-(4-(5-(2-(1-(3,5-dichlorophenyl)cyclohexyl)ethyl)-1,2,4-oxadiazol-3-yl)phenyl)-3-hydroxyazetidine-1-carboxylate

Ausbeute 75.2%

Lösungsmittel

ethyl acetate

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   TemperaturThe mixture was heated to 80° C. overnight
2. 2
   Waschenwashed with saturated aqueous NaCl solution
3. 3
   TrocknenThe organic layer was dried (MgSO4)
4. 4
   Filtrationfiltered
5. 5
   Einengenconcentrated
6. 6
   SonstigeThe crude product was purified on a 24 g ISCO cartridge
7. 7
   Wascheneluted with EtOAc-hexanes gradient

Vorschrift

BOP-Cl (36.4 mg, 0.143 mmol) was added to a mixture of crude tert-butyl 3-hydroxy-3-(4-(N′-hydroxycarbamimidoyl)phenyl)azetidine-1-carboxylate (Intermediate 4, 40 mg, 0.13 mmol), 3-(1-(3,5-dichlorophenyl)cyclohexyl)propanoic acid (39.2 mg, 0.13 mmol) and diisopropylethyl amine (0.045 mL, 0.26 mmol) in DMF (3 mL). The mixture was stirred at room temperature for 2 h, and a 1M solution of tetra-n-butylammonium fluoride in THF (0.13 mL, 0.13 mmol) was added. The mixture was heated to 80° C. overnight, diluted with ethyl acetate, and washed with saturated aqueous NaCl solution. The organic layer was dried (MgSO4), filtered, and concentrated. The crude product was purified on a 24 g ISCO cartridge and eluted with EtOAc-hexanes gradient to obtain tert-butyl 3-(4-(5-(2-(1-(3,5-dichlorophenyl)cyclohexyl)ethyl)-1,2,4-oxadiazol-3-yl)phenyl)-3-hydroxyazetidine-1-carboxylate (56 mg, 50% yield, HPLC purity: 80%). HPLC retention time=4.71 minutes (Waters Sunfire C18 4.6×50 mm) eluting with 10-90% aqueous methanol with 0.1% TFA over a 4 minute gradient. LC/MS: m/e 572.25 (M+H)+.

Quelle