2-chloro-6-(pyrrolidin-1-yl)benzaldehyde synthesis

Yield:110405-86-2 53%

Reaction Conditions:

with potassium carbonate in dimethyl sulfoxide at 100;

Steps:

52.1 Step 1: Preparation of 2-chloro-6-(pyrrolidin-l-yl)benzaldehyde

A 100 mL round-bottom flask was charged with 2-chloro-6-fluorobenzaldehyde (2.00 g, 12.6 mmol, 1.00 equiv), pyrrolidine (1.34 g, 18.8 mmol, 1.49 equiv), potassium carbonate (4.34 g, 31.4 mmol, 2.49 equiv), and dimethyl sulfoxide (20 mL). The resulting solution was stirred overnight at 100 °C in an oil bath. Then diluted with ]0 (20 mL). The resulting solution was extracted with dichloromethane (3 x 20 mL) and the organic layers were combined, washed with H₂0 (3 x 10 mL), dried over anhydrous sodium sulfate, filtered and concentrated under reduced pressure. The residue was chromatographed on a silica gel column with ethyl acetate/petroleum ether (1/15) to yield 1.40 g (53% yield) of 2-chloro-6-(pyrrolidin- l-yl)benzaldehyde as a yellow solid. ^XH NMR 300 MHz (CDC1₃) δ 10.49 (s, 1H), 7.20-7.25 (m, 1H), 6.73-6.78 (m, 2H), 3.14-3.19 (m, 4H), 1.94-2.02 (m, 4H). LCMS (ESI, m/z): 210 [M+H]⁺.

References:

WO2013/103973,2013,A1 Location in patent:Paragraph 00207