6'-Bromo-1'H-spiro[cyclopropane-1,3'-indole]-2'-one synthesis

Yield:1378865-57-6 92%

Reaction Conditions:

Stage #1:6-bromo-2,3-dihydro-1H-indole-2-one with n-butyllithium;diisopropylamine in tetrahydrofuran;hexane at -40; for 0.75 h;
Stage #2:ethylene dibromide in tetrahydrofuran;hexane at -40 - 20; for 16 h;

Steps:

1.1a 6'-bromospiro[cyclopropane-1,3'-indolin]-2'-one
n-Butyllithium (2.25 M in hexane, 130 mL, 259.4 mmol) was added drop wise at -40°C to a solution of 6-bromoindolin-2-one (25.0 g, 117.9 mmol) and diisopropylamine (36.54 mL, 259.4 mmol) in THF (500 mL).The mixture was stirred for 45 mm at that temperature, 1,2-dibromoethane (31.0 mL, 353.7 mmol) wasadded drop wise and stirring was continued for 16 h while the temperature was slowly raised to RT. Thereaction mixture was quenched with 4 N HCI (400 mL) and the aqueous part was separated andextracted with EtOAc (3x 100 mL). The combined organic layers were washed with brine and dried overNa2504. The solvents were evaporated and the residue was triturated with EtOAchexane (1:4, 200 mL),filtered and washed with EtOAc/hexane (1:4, 100 mL). Brown solid. Yield: 26.0 g (92%). HPLC (method 1): R = 2.92 mi mlz [M+H] = 240.0 (MW calc. 238.08)

References:

GRÜNENTHAL GMBH;KONETZKI, Ingo;JAKOB, Florian;WAGENER, Markus;WELBERS, André;HESSLINGER, Christian WO2017/108203, 2017, A1 Location in patent:Page/Page column 30; 35; 36

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