2-benzyl-7-bromo-3H-isoindol-1-one synthesis

Yield:877150-62-4 73%

Reaction Conditions:

Stage #1: 7-bromo-2,3-dihydro-1H-isoindol-1-onewith caesium carbonate in acetonitrile at 20; for 0.25 h;
Stage #2: benzyl bromide in acetonitrile at 0 - 20; for 16 h;

Steps:

23.1 Step 1: 2-Benzyl-7-bromoisoindolin-l-one (2)

[00309] To a solution of 7-bromoisoindolin-l-one 1 (212 mg, 1.0 mmol) in MeCN (5.0 mL) was added CS2CO3 (652 mg, 2.0 mmol). The reaction mixture was stirred at rt for 15 min then cooled to 0-5 °C. Benzyl bromide (274 mg, 1.6 mmol) was added dropwise. The reaction mixture was allowed to warm to rt and stirred for 16 h. The mixture was partitioned between EtOAc and water and the aqueous layer extracted with EtOAc. The combined organic layers were washed with water and brine, dried (Na₂S0₄), filtered, and concentrated under reduced pressure. The residue was purified (silica gel; eluting with 20% EtOAc in hexanes) to afford compound 2 (220 mg, 73%) as a yellow solid. 1H MR (400 MHz, CD₃OD): δ 7.68 (m, 1H), 7.46 - 7.54 (m, 2H), 7.32 - 7.41 (m, 5H), 4.83 (s, 2H), 4.37 (s, 2H).

References:

WO2019/70742,2019,A1 Location in patent:Paragraph 00309