2-cyclopropyloxazole-4-carbonitrile synthesis

Yield:-

Reaction Conditions:

Stage #1: 4-cyclopropyl-4-ethoxy-3-azabut-3-enenitrile;formic acid ethyl esterwith potassium tert-butylate in tetrahydrofuran at -10;
Stage #2: with acetic acid for 0.0333333 h;Heating / reflux;

Steps:

To a solution of N-cyanomethyl-cyclopropanecarboximidic acid ethyl ester (4.54 g, 14.9 mmol) in THF (10 mL) at -10 °C were added potassium t?rt-butoxide (1.67 g, 14.9 mmol) and ethyl formate (1.2 mL, 14.9 mmol) successively. After being stirred at -10 °C for 3 h, the reaction mixture was left in the refrigerator overnight and then diluted with ether. The precipitated brown solid was filtered and dried under vacuum. The vacuum-dried solid was added to boiling acetic acid (45 mL) and refluxed for 2 min. The reaction mixture was cooled to room temperature, diluted with water, and adjusted to pH 7 by adding 1 N sodium hydroxide. The reaction mixture was extracted with ether (2 x 1 L). The combined organic fractions were dried (MgSO₄), filtered, and concentrated. The crude brownish solid was chromatographed (silica gel, 0-50%EtOAc in Hexane, detection KMnO₄ spray, R_f = 0.3 in 10% EtOAc/ Hexane) to give 2-cyclopropyl- oxazole-4-carbonitrile as a colorless liquid (463 mg).

References:

WO2009/70485,2009,A1 Location in patent:Page/Page column 136-137