Yield:76575-71-8 26%

Reaction Conditions:

Stage #1: but-2-enenitrilewith pyridine;chlorine at 0 - 13;
Stage #2: Methyl thioglycolatewith potassium carbonate in methanol at 10 - 20; for 5 h;

Steps:

4

A mixture of cis- and frans-crotononitrile 4a (298.00 g, 4.44 mol) was mixed with pyridine (61.49 g, 0.78 mol) and the resulting mixture was cooled to 0⁰C. Chlorine (314.92 g, 4.44 mol) was passed through the mixture at a rate of 60-65 g/h to maintain the internal temperature at 10-13 ⁰C. When the addition was complete the reaction mixture was allowed to warm up to room temperature and mixed overnight. The resulting oil was dissolved in CH₂CI₂ (1.5 L) and the solution was passed through a silica gel plug. The filtrate was concentrated in vacuo to give a complex reaction mixture (508.61 g) as brownish oil. This oil (493.80 g) was mixed with methyl thioglycolate (422.77 g, 3.98 mol) and the resulting solution was added slowly (1.5 h) to a slurry of K₂CO₃ (1651 g, 11.95 mol) in methanol (2.2 L) at 10⁰C. The final slurry was allowed to warm up to room temperature and was stirred at ambient temperature for 5 h. Salts were filtered out and washed with methanol (2 L). The organic solutions were combined and evaporated. The residue was redissolved in ethyl acetate (3 L) and passed through a silica gel plug. The plug was washed with extra ethyl acetate (2 L). The solutions were combined and the solvent was evaporated in vacuo to give brown oil (627 g). The mixture was vacuum distilled at 6 mmHg. An oil that distilled at 138 ⁰C crystallized in the receiving flask (303.07 g). Recrystallizion from methanol yielded 4b (179.00 g, 26%) as white crystals. ¹H NMR (CDCI₃, 400 MHz) δ 6.25 (s, 1H), 5.30 (bs, 2H), 3.81 (s, 3H), 2.37 (s, 3H). ¹³C NMR (CDCI₃, 100 MHz) 5 165.2, 154.5, 147.2, 119.0, 99.3, 51.4, 16.5.

References:

WO2007/23382,2007,A2 Location in patent:Page/Page column 64