Yield: 3.3 g

Reaction Conditions:

with piperidine;pyridine at 100; for 3 h;

Steps:

7.1 Step 1: 3-(3-bromo-4-fluoro-phenyl)-acrylic acid
3-Bromo-4-fluoro-benzaldehyde (5.0 g, 24.6 mmol), malonic acid (5.6 g, 53.7 mmol), and piperidine (0.5 mL, 4.9 mmol) were added to pyridine (11.4 mL). The reaction mixture was stirred at 100° C. for 3 hours and then concentrated under reduced pressure. Distilled water was added to the reaction mixture, which was then filtered. The resulting solid was recrystallized from ethanol to give 3.3 g of the titled compound as a white solid. (0154) ¹H NMR (400 MHz, CD₃OD) 7.93 (d, 1H), 7.64-7.60 (m, 2H), 7.27 (t, 1H), 6.49 (d, 1H)

References:

YUHAN CORPORATION;Park, Chan-Sun;Kim, Young-Hwan;Lee, Gyu-Jin;Hur, Youn;Jung, Eun-Hye;Tak, Hee-Jae;Shin, Seung-Yub;Lee, Ho-Jin;Lee, Chun-Ho;Lee, Koo-Yeon US2015/291563, 2015, A1 Location in patent:Paragraph 0153; 0154