Diethyl (cyanomethyl)phosphonate → HCID 69205138, compound

To a stirred solution of cyanomethylphosphonic acid diethyl ester (1.3 mL, 8.3 mmol) in THF (10 mL) in an ice bath was added lithium bis(trimethylsilyl)amide (1.0 M solution in THF, 8.2 mL, 8.2 mmol) dropwise. The mixture was stirred at room temperature for 40 min. A solution of (3,4-dihydro-2H-benzo[b][1,4]dioxepin-7-yl)-(3,5-dimethoxy-phenyl)-methanone (1.3 g, 4.1 mmol) in anhydrous THF (10 mL) was added to the mixture. The mixture was refluxed overnight. The solution was poured into ice water (20 mL). The aqueous layer was extracted with ethyl acetate (2×50 mL). The combined organic layers was washed with water (50 mL), sodium hydrogen carbonate (50 mL, sat), brine (50 mL) and dried over magnesium sulfate. Removal of solvent and chromatography (Silica Gel) gave a mixture of (E/Z) 3-(3,4-dihydro-2H-benzo[b][1,4]dioxepin-7-yl)-3-(3,5-dimethoxy-phenyl)-acrylonitrile as an oil (1.23 g, 89% yield): 1H NMR (DMSO-d6) δ 2.09-2.16 (m, 4H, 2CH2), 3.73 (s, 6H, 2CH3), 4.12-4.25 (m, 8H, 4CH2), 6.24 (s, 1H, CH), 6.30 (s, 1H, CH), 6.44-6.45 (m, 4H, Ar), 6.62-6.65 (m, 2H, Ar), 6.93-7.09 (m, 6H, Ar); 13C NMR (DMSO-d6) δ 30.97, 31.13, 55.40, 70.37, 70.52, 95.05, 95.87, 100.90, 101.82, 106.72, 107.06, 118.06, 118.12, 121.09, 121.61, 121.64, 122.39, 123.41, 124.47, 131.71, 132.26, 138.98, 140.12, 150.42, 150.55, 152.09, 152.89, 160.31, 160.39, 160.43.

1. temperatureThe mixture was refluxed overnight
2. extractionThe aqueous layer was extracted with ethyl acetate (2×50 mL)
3. washThe combined organic layers was washed with water (50 mL), sodium hydrogen carbonate (50 mL, sat), brine (50 mL)
4. dry with materialdried over magnesium sulfate
5. customRemoval of solvent and chromatography (Silica Gel)
6. customgave

ORD record

ord-0575a70ea7bc4c5db4231dd4ac2cf418

Source dataset

uspto-grants-2008_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07470723B2