[H-].[Na+].P(=O)([O-])O[C:5]([CH2:17][CH3:18])(CC)[C:6]1[CH:11]=[CH:10][C:9]([F:12])=[CH:8][C:7]=1[C:13]#[N:14].[F:21][C:22]1[CH:29]=[CH:28]C(C=O)=[CH:24][CH:23]=1.[Na+].[Cl-]>CN(C=O)C.O>[F:21][C:22]1[CH:29]=[CH:28][C:18]([CH:17]=[CH:5][C:6]2[CH:11]=[CH:10][C:9]([F:12])=[CH:8][C:7]=2[C:13]#[N:14])=[CH:24][CH:23]=1
Sodium hydride (60% in mineral oil; 1.66 g [0.993 g NaH], 1.4 mmol, 1.10 equiv) was added to a solution of diethyl-2-cyano-4-fluorobenzyl phosphonate (10.2 g-equiv, 37.6 mmol, 1.0 equiv) in DMF (40 mL) over a period of 2 min. The reaction was stirred for 20 min at room temperature. 4-Fluorobenzaldehyde (4.67 g, 38 mmol, 1.0 equiv) was then added over a period of 2 min. After stirring for 18 h, H2O (200 mL) and satd. NaCl (50 mL) were added and the resulting mixture was extracted with EtOAc (2×100 mL). The combined organic layers were washed with 1N NaOH (1×100 mL) and H2O (2×100 mL), dried (anhyd. Na2SO4), and rotary evaporated (>100° C., heat gun). The crude, dark-red crystalline/oil (7.49 g, 82.7%) was chromatographed twice on silica gel (50×250 mm, dry pack), eluting first with hexane/EtOAc [4:1] and the second chromatography with [30:1] to provide a TLC-pure, yellow compound (2.1 g, 23.2%).
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