7'-fluoro-Spiro[cyclopropane-1,3'-[3H]indol]-2'(1'H)-one synthesis

Yield:872141-30-5 54%

Reaction Conditions:

Stage #1: 7-fluoroindolin-2-onewith lithium dipropan-2-ylazanide in tetrahydrofuran at -40; for 0.5 h;
Stage #2: ethylene dibromide in tetrahydrofuran at 20; for 24 h;

Steps:

3 Intermediate Preparation Example 3: Synthesis of 7'-fluorospiro[cyclopropane-1,3'-indoline]-2'-one (P-3)

7-Fluorindolin-2-one (0.3g, 2mmol) was dissolved in anhydrous tetrahydrofuran (3mL), cooled to -40°C, LDA (2mol/L, 4mL, 8mmol) was added, stirred for 30min, and heated to 0 , 1,2-dibromoethane (1.14 g, 6 mmol) was added, and the reaction was carried out at room temperature for 24 h. Saturated aqueous ammonium chloride solution (5 mL) and water (15 mL) were added to the reaction system, extracted twice with ethyl acetate (10 mL each time), the organic phases were combined, washed once with saturated brine, dried over anhydrous sodium sulfate, filtered, and reduced in pressure. After concentration, the concentrate was purified by silica gel column chromatography (petroleum ether/ethyl acetate=4:1) to obtain the title compound (0.19 g, 54%).

References:

WO2022/156351,2022,A1 Location in patent:Page/Page column 23