Reaction #657264

Reaction equation

aniline

MeCN

Quinoline-8-carbonyl chloride

quinoline-8-carboxylic acid

thionyl chloride

triethylamine

→

N-[4-((3aR,4S,7R,7aS)-1,3,3a,4,7,7a-hexahydro-1,3-dioxo-4,7-methano-2H-isoindol-2-yl)phenyl]-quinoline-8-carboxamide

Yield 87.0%

Conditions

Workup

1. 1
   Concentrationconcentrated in a vacuum
2. 2
   Otherpurified by flash chromatography (toluene/EtOAc/acetone 6/3/1 Rf 0.5)
3. 3
   OtherThe product was obtained as an off-white solid with 87% yield (140 mg)

Procedure

Quinoline-8-carbonyl chloride was freshly prepared by heating 135 mg (0.78 mmol) of quinoline-8-carboxylic acid in an excess of thionyl chloride (622 μL) for three hours at 60-70° C. This mixture was added dropwise to a solution of 100 mg of the aniline precursor from step b (0.39 mmol) and 5 equivalents of triethylamine (1.95 mmol) in 7 mL of dry MeCN. The reaction mixture was stirred at room temperature for three days, concentrated in a vacuum and purified by flash chromatography (toluene/EtOAc/acetone 6/3/1 Rf 0.5). The product was obtained as an off-white solid with 87% yield (140 mg). LC-MS (1000 (+)-5.5-254-80:20): Rt 3.45 min, 412 [M+H]+ >99% at 254 nM; 1H NMR (300 MHz, CDCl3): 1.48-1.75 (m, 6H), 2.88 (me, 2H), 3.25 (me, 2H), 7.27-7.32 (m, 2H), 7.56 (dd, J=4.3, 8.3 Hz, 1H), 7.74 (dd, J=7.45, 7.50 Hz, 1H), 7.98-8.03 (m, 2H), 8.02 (br d, J=1.6 Hz, 1H), 8.34 (dd, J=1.8, 8.4 Hz, 1H), 8.96 (dd, J=1.6, 7.4 Hz, 1H), 9.01 (dd, J=1.8, 4.3 Hz, 1H).

Source