3-(5-bromofuran-2-yl)-3-oxopropanenitrile

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Following the method of Rudorf and Augustin (Phosphorus and Sulfur 1981, 9, 329), a solution of 3.02 g (14.1 mmol) 3-(5-bromo-furan-2-yl)-3-oxo-propionitrile in 25 ml dry DMSO was added dropwise to a stirred suspension of 1.13 g (28.3 mmol, 60% dispersion in mineral oil) sodium hydride in 25 ml DMSO under argon at room temperature. 0.85 ml (14.1 mmol) carbon disulfide was then added dropwise, with external water bath cooling, and stirring continued for 2 hour, after which 1.8 ml (28.3 mmol) methyl iodide was added dropwise, with external water bath cooling, and stirring continued for a further 16 h. The reaction mixture was then poured into 1 l ice-cold water, and the precipitate collected by filtration, washed with hexane, and dried in vacuo to afford 2.91 g (65%) 2-(5-bromo-furan-2-carbonyl)-3,3-bis-methylsulfanyl-acrylonitrile as a yellow crystalline solid. EI-MS m/e (%): 319 (M{81Br}+, 10), 317 (M{79Br}+, 10), 304 ([M{81Br}-CH3]+, 30), 302 ([M{79Br}-CH3]+, 45), 238 ([M—Br]+, 100), 223 (26), 210 (38), 195 (29), 175 (76), 173 (79), 95 (39), 38 (36). cooling cooling stirring continued for a further 16 h the precipitate collected by filtration washed with hexane dried in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To 1.95 g (48.8 mmol, 60% dispersion in mineral oil) sodium hydride in a 2-necked flask fitted with a reflux condenser was added dropwise 30 ml THF and the mixture was then heated to reflux. A solution of 6.4 ml (122 mmol) acetonitrile and 5.00 g (24.4 mmol) 5-bromo-furan-2-carboxylic acid methyl ester in 20 ml dry THF was added dropwise and the reaction mixture heated at reflux for 5 hours. The reaction mixture was then cannulated into a rapidly stirred solution of 1M hydrochloric acid at 0° C. The mixture was extracted twice with ethyl acetate and the combined organic phases dried over sodium sulfate and concentrated in vacuo. Chromatography (ethyl acetate/hexane 2/3) afforded 3.90 g (75%) 3-(5-bromo-furan-2-yl)-3-oxo-propionitrile as a yellow crystalline solid. EI-MS m/e (%): 215 (M{81Br}+, 27), 213 (M{79Br}+, 28), 175 ([M{81Br}—CH2CN]+, 100), 173 ([M{79Br}—CH2CN]+, 100), 38 (59). the mixture was then heated to reflux the reaction mixture heated at reflux for 5 hours The mixture was extracted twice with ethyl acetate the combined organic phases dried over sodium sulfate concentrated in vacuo