[H-].[Na+].[C:3]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])(=[O:12])[CH2:4][C:5]([O:7][C:8]([CH3:11])([CH3:10])[CH3:9])=[O:6].[H][H].[Cl:20][C:21]1[C:22](F)=[CH:23][C:24]([F:29])=[C:25]([CH:28]=1)[C:26]#[N:27]>CN(C=O)C.CCOCC>[Cl:20][C:21]1[CH:28]=[C:25]([C:26]#[N:27])[C:24]([F:29])=[CH:23][C:22]=1[CH:4]([C:5]([O:7][C:8]([CH3:9])([CH3:10])[CH3:11])=[O:6])[C:3]([O:13][C:14]([CH3:17])([CH3:16])[CH3:15])=[O:12]
To sodium hydride (60% in mineral oil, 3.75 g, 94 mmol) under nitrogen was added dry DMF (150 mL) and the suspension was cooled in an ice bath. Di-t-butyl malonate (8.1 g, 37.5 mmol) was added dropwise over 15 minutes via syringe with hydrogen evolution. The suspension was stirred for 30 minutes after which time 5-chloro-2,4-difluorobenzonitrile (5.0 g, 28.8 mmol) in DMF (10 mL) was added dropwise over 15 minutes and the reaction was heated to 80° C. for 12 hours when TLC (15% ethyl acetate/hexanes) indicated mostly product. The reaction was diluted with ether and quenched into water containing aq. ammonium chloride. The mixture was extracted twice with ethyl acetate and the organic layers were washed with brine, dried over sodium sulfate and concentrated in vacuo. The residue was purified on silica gel (2-10% ethyl acetate/hexanes) to give the title product. NMR indicated about a 6:1 mixture of product and the isomeric di-t-butyl, 2-(4-chloro-2-cyano-5-fluorophenyl)malonate. 1H-NMR (400 MHz, CDCl3) δ ppm 1.46 (s, 18H), 5.05 (s, 1H), 7.55 (d, J=8.3 Hz, 1H), 7.71 (d, J=6.0, 1H) (major isomer) and 1.46 (s, 18H), 4.95 (s, 1H), 7.63 (d, J=8.3 Hz, 1H), 7.78 (d, J=6.0, 1H) (minor isomer).
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