Cyanoacetic acid - commercial, 98% pure

Tert butyl methyl ether , commercial 98% pure

Concentrated sulfuric acid, Lab reagent, SD Fine Chem.

To a well-stirred mixture of cyanoacetic acid (80 mmol) in tert butyl methyl ether (TBME, 50 mL) at about 10­ºC was added sulfuric acid (18 g, 10 mL) in 10 min time. The mixture was then stirred at room temperature for 10–12 h. The reaction mixture was added to 20% sodium carbonate solution (100 mL). The reaction mass was extracted in TBME or dichloromethane (50 mL × 2). The combined organic layer was washed with water (100 mL), dried over sodium sulfate and concentrated under reduced pressure to obtain the product (94–98%). Most examples gave NMR pure product. This can be scaled up to 1 kg batches.

¹H NMR ( CDCl₃; 400MHz ):- δ 7.29 ( s, 1H, NH ), 3.74 ( s, 3H, OCH₃ ), 1.36 ( s, 9H, -(CH₃)₃); ¹³C NMR ( CDCl₃; 100 MHz):- 170.0, 163.8, 52.1, 51.2, 41.9, 28.4.

One pot esterification and Ritter reaction: Chemo and regioselectivity from tert-butyl methyl ether.

Tetrahedron Lett, 2011, 52, 4262-4265