Sodium Bicarbonate → (11S)-11-isopropyl-10,11-dihydro-8H-[1,4]oxazino[4',3':1,2]imidazo[4,5-c]quinoline

Participants

Reaction Conditions

Reaction Steps

1-[(1S)-1-({[tert-Butyl(dimethyl)silyl]oxy}methyl)-2-methylpropyl]-2-(chloromethyl)-1H-imidazo[4,5-c]quinoline (4.85 g, 11.6 mmol) was dissolved in 110 mL of tetrahydrofuran (THF) and the solution was cooled to −78° C. under N2. A 1.0 M solution of tetrabutylammonium fluoride in THF (12.8 mL) was added and the reaction mixture was allowed to warm to 0° C. overnight. The reaction mixture was then treated with 50 mL of saturated sodium bicarbonate solution and 100 mL of CHCl3. The layers were separated and the organic portion was washed with H2O (50 mL) and brine (4×25 mL). The organic layer was dried over Na2SO4, filtered and concentrated under reduced pressure to give a yellow syrup. The syrup was concentrated from toluene (3×) to give a pale yellow foam. This material was dissolved in 100 mL of anhydrous THF and the solution was cooled 0° C. and stirred under N2. Solid potassium tert-butoxide was then added and the reaction mixture was allowed to warm to ambient overnight. The THF was then removed under reduced pressure and the resulting material was partitioned between 100 mL of CHCl3 and 100 mL of saturated sodium bicarbonate solution. The layers were separated and the organic portion was washed with H2O and brine. The organic portion was then dried over Na2SO4, filtered and concentrated under reduced to give brown foam. Chromatography (SiO2, 0%-50% 80:18:2 CHCl3/methanol/concentrated NH4OH(CMA) in CHCl3) gave (11S)-11-isopropyl-10,11-dihydro-8H-[1,4]oxazino[4′,3′:1,2]imidazo[4,5-c]quinoline (2.13 g) as a light yellow solid.

Provenance & Evidence