Chloroacetyl chloride → (11S)-11-[(benzyloxy)methyl]-10,11-dihydro-8H-[1,4]oxazino[4',3':1,2]imidazo[4,5-c]quinoline

Participants

Reaction Steps

Chloroacetyl chloride (14.8 mL, 186 mol) was added to a mixture of (2R)-2-[(3-aminoquinolin-4-yl)amino]-3-(benzyloxy)propan-1-ol (28 g, 86 mmol) and triethylamine (12.0 mL, 86.5 mmol) dissolved in 432 mL of CH2Cl2 at 0° C. The reaction was stirred for 1 hour at ambient temperature. The solvent was removed under reduced pressure and the resulting dark, oily solid was treated with acetic acid (400 mL). The mixture was heated to reflux for 6 hours. The reaction was cooled to ambient temperature and the acetic acid was removed under reduced pressure. The resulting dark brown oil was concentrated from toluene (2×) and then from ethanol to afford a dark brown oil. The oil was dissolved in a mixture of ethanol (400 mL) and water (60 mL) and treated with potassium carbonate (60 g). The reaction mixture was heated at 60° C. and stirred for 1 hour. The reaction was then cooled to ambient temperature and filtered. The filtrate was concentrated under reduced pressure to afford a dark oil. Chromatography (SiO2, 0-30% CMA/CHCl3) gave 17 g of (11S)-11-[(benzyloxy)methyl]-10,11-dihydro-8H-[1,4]oxazino[4′,3′:1,2]imidazo[4,5-c]quinoline as a light brown oil.

Provenance & Evidence