Reaktion #166923

Reaktionsgleichung

2-Amino-1-(4-bromo-phenyl)-ethanone HCl

1-tert-butoxycarbonylamino-cyclopropanecarboxylic acid

HATU

DIPEA

→

{1-[2-(4-bromo-phenyl)-2-oxo-ethylcarbamoyl]-cyclopropyl}-carbamic acid tert-butyl ester

Ausbeute 90.0%

Lösungsmittel

DMF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Einengenconcentrated
2. 2
   workup.ADDITIONThe mixture was diluted with EtOAc (25 mL)
3. 3
   Waschenwashed with saturated NaHCO3 (3 10 mL), H2O (10 mL), and brine (10 mL)
4. 4
   TrocknenThe solution was dried over MgSO4

Vorschrift

2-Amino-1-(4-bromo-phenyl)-ethanone HCl (2.5 g, 10 mmol) in DMF (30 mL) was treated with 1-tert-butoxycarbonylamino-cyclopropanecarboxylic acid (1.97 g, 9.8 mmol), HATU (4.02 g, 10.5 mmol), and DIPEA (5.6 mL, 31.1 mmol). The mixture was stirred for 18 hours and concentrated. The mixture was diluted with EtOAc (25 mL), and washed with saturated NaHCO3 (3 10 mL), H2O (10 mL), and brine (10 mL). The solution was dried over MgSO4 and subjected to a 80 g SiO2 COMBIFLASH column (0-100% EtOAc-hexanes gradient) to afford {1-[2-(4-bromo-phenyl)-2-oxo-ethylcarbamoyl]-cyclopropyl}-carbamic acid tert-butyl ester (3.49 g, 90%). This material (3.49 g, 8.8 mmol) in xylenes (20 mL) was treated with ammonium acetate (3.4 g, 44 mmol). The reaction was stirred at 130° C. in a sealed tube for 18 hours. The mixture was concentrated and suspended in dicholormethane (100 mL) and washed with saturated NaHCO3 (50 mL). The solution was dried over MgSO4 to afford crude {1-[5-(4-bromo-phenyl)-1H-imidazol-2-yl]-cyclopropyl}-carbamic acid tert-butyl ester, which was used without further purification: MS (ESI) m/z 379 [M+H]+.

Quelle