Yield:540778-86-7 90%

Reaction Conditions:

with potassium carbonate in tetrahydrofuran;

Steps:

11.1 Step 1

Step 1 Ethyl (E)-3-bromo-4-fluorocinnamate To a suspension of 5.36 g (26.4 mmol) of 3-bromo-4-fluorobenzaldehyde and 11.82 g (85.5 mmol) of K₂CO₃ in 100 ml of anhydrous THF under Ar, 13.0 ml (65.5 mmol) of triethyl phosphonoacetate was added. The reaction mixture was stirred at room temperature for 4 days at which time the reaction was complete. The mixture was extracted with EtOAc, washed with brine and water, dried (MgSO₄), filtered, and concentrated. Flash column chromatography (10% EtOAc/hexane) yielded a white solid (6.49 g, 90%): m.p. 64-65° C.: R_f 0.60 (20% EtOAc/hexane). ¹H NMR (400 MHz, CDCl₃) δ1.34 (t, J=6.8 Hz, 3, CH₃), 4.26 (q, J=6.8 Hz, 2, CH₂), 6.36 (d, J=15.6 Hz, 1, HC=CCO), 7.13 (t, J=8.4 Hz, 1, ArH), 7.44 (m, 1, ArH), 7.57 (d, J=16.0 Hz, 1, C=CHCO), 7.72 ppm (dd, J=8.0, 2.0 Hz, 1, ArH).

References:

US2003/176506,2003,A1