(Z)-ethyl 4,4,4-trifluoro-3-oxo-2-(2-phenylhydrazono)butanoate synthesis

Yield:73981-89-2 83%

Reaction Conditions:

with hydrogenchloride;copper diacetate;sodium nitrite in water;acetone at 10;

Steps:

General Procedures for synthesis of compounds 3.

General procedure: To 60 ml of asolution of amine (40 mmol) in 1 M hydrochloric acid, a solution of sodium nitrite (2.76 g, 40 mmol) in 40 ml of water at 0 °C was added dropwise. Then, in another container, solutions of copper (II) acetate(20 mmol) in water (20 ml) and 3-oxo ester 1 (40 mmol) in acetone (20 ml) were mixed. To the resulting suspension, a solution of the aryldiazonium salt 2 was slowly added dropwise at 10 °C. The resulting product 3 was extracted by chloroform (2 20 ml), and the chloroform layer was separated and dried with anhydrous sodium sulfate. The chloroform was removed in vacuo, and compound 3 was recrystallized from ethanol.Ethyl (2Z)-4,4,4-trifluoro-3-oxo-2-(2-phenylhydrazinylidene)butanoate(3a) was obtained according to the general procedure from 3-oxo ester 1a (7.36 g, 40 mmol) and benzenediazonium chloride prepared from aniline (3.75 g, 40mmol) as a yellow powder (9.56 g, 83%yield), mp 90-91 °C [53,77]. 1H NMR (400 MHz, DMSO-d6): δ 1.32 (t,3JH,H 7.1 Hz, 3H, OCH2Me), 4.36 (q, 3JH,H 7.1 Hz, 2H, OCH2Me),7.25-7.28, 7.46-7.50, 7.56-7.58 (allm, 4H, C6H4),12.95 (s,1H,NH).19FNMR (470 MHz, DMSO-d6): δ 93.35 (s, CF3).

References:

Makhaeva, Galina F.;Lushchekina, Sofya V.;Boltneva, Natalia P.;Serebryakova, Olga G.;Kovaleva, Nadezhda V.;Rudakova, Elena V.;Elkina, Natalia A.;Shchegolkov, Evgeny V.;Burgart, Yanina V.;Stupina, Tatyana S.;Terentiev, Alexey A.;Radchenko, Eugene V.;Palyulin, Vladimir A.;Saloutin, Victor I.;Bachurin, Sergey O.;Richardson, Rudy J. [European Journal of Medicinal Chemistry,2021,vol. 218,art. no. 113385]