3,4-dihydro-6-iodo-1(2H)-Isoquinolinone synthesis

Yield:877868-87-6 8.15 g (45%)

Reaction Conditions:

Stage #1: 6-bromo-3,4-dihydroisoquinolin-1(2H)-onewith n-butyllithium in tetrahydrofuran at -78; for 1 h;
Stage #2: with iodine in tetrahydrofuran at -78; for 1.5 h;

Steps:

143.1 Step 1:

Step 1: 6-Iodo-3,4-dihydroisoquinolin-1(2H)-one A solution of 6-bromo-3,4-dihydroisoquinolin-1(2H)-one (15 g, 66.35 mol) in dry THF (1.0 L) cooled to -78° C. and added n-butyl lithium (1.1 M, 151 mL, 166 mol) slowly into the reaction mixture. The reaction mixture was stirred at -78° C. for 1 h. Then iodine (67.1 g, 265.4 mol) in THF was slowly added dropwise at -78° C. The reaction mixture was stirred for another 1.5 h at -78° C. The reaction mixture was quenched with ammonium chloride solution and extracted with ethyl acetate & washed with water, brain solutions and dried over sodium sulfate and concentrated in vacuo. The crude product was purified by column chromatography (Silica, 1-75% ethyl acetate in hexane) to afford 8.15 g (45%) of the title product as a white solid, mp>300° C.; (ES) m/z 273.1 [M +H]⁺.

References:

US2009/69300,2009,A1 Location in patent:Page/Page column 37-38