Isoamyl Nitrite → Tert-butyl(1-(4-(6-(hydroxyimino)-5-oxo-3-phenyl-5,6,7,8-tetrahydroquinolin-2-yl)phenyl)cyclobutyl)carbamate

Participants

Reaction Steps

To a solution of tert-butyl(1-(4-(5-oxo-3-phenyl-5,6,7,8-tetrahydroquinolin-2-yl)phenyl)cyclobutyl)carbamate (1.00 g, 2.134 mmol) in anhydrous THF (30 mL) was added dropwise potassium tert-butoxide (1M in THF, 2.56 ml, 2.56 mmol) over a period of 10 min to give a deep red solution. The reaction mixture was stirred at room temperature under a nitrogen atmosphere for 30 min. To this was added dropwise isopentyl nitrite (0.286 ml, 2.134 mmol) over a period of 5 min to give a red solution. The reaction mixture was stirred at 50° C. under a nitrogen atmosphere for 1 hour then allowed to cool to room temperature and concentrated to dryness under reduced pressure. The residue was redissolved in water (5 mL), acidified with 1M HCl solution (5 mL) and extracted into ethyl acetate (3×10 mL). The combined organic phases were washed with water (20 mL), brine (20 mL), dried over Na2SO4, filtered and concentrated to dryness under reduced pressure. The residue was purified via Biotage chromatography (silica, hexane:ethyl acetate, gradient elution from 88:12 to 0:100) to give the desired product as a brown solid (436 mg, 41% yield)). 1H-NMR (500 MHz, CDCl3) δ 8.40 (1H, s), 7.40 (2H, d), 7.32 (2H, d), 7.25-7.29 (3H, m), 7.18-7.22 (2H, m), 5.04 (1H, br s), 3.38 (2H, t), 3.29 (2H, t), 2.26-2.59 (4H, br m), 2.01-2.12 (1H, m), 1.76-1.86 (1H, m), 1.15-1.45 (9H, br m). LCMS (Method A) RT=6.74 min, M+H+=498.13.

Provenance & Evidence