EthaniMidaMide, N-(4-broMo-2,6-difluorophenyl)-N'-(1-Methylethyl)- synthesis

Yield:-

Reaction Conditions:

with triethylamine;trichlorophosphate in toluene for 3 h;Product distribution / selectivity;Reflux;

Steps:

30
Preparation 30N-(4-Bromo-2,6-difluoro-phenyl)-N'-isopropyl-acetamidineAdd TEA (10.05 mL) to a mixture of 4-bromo-2,6-difluoro-phenylamine (10.0 g), N-isopropyl acetamide (9.73 g), phosphoryl chloride (6.70 mL) in toluene (150 mL). Heat the mixture to reflux for 3 h. Cool the mixture and remove the solvent under vacuum. Dissolve the crude in DCM, wash with an aqueous saturated solution of sodium bicarbonate several times to remove all traces of acid. Dry over sodium sulfate and remove the solvent under vacuum to afford 14 g of the title compound. MS (ES⁺): m/z=292 (M+H)⁺.

References:

COATES, David A.;GELBERT, Lawrence Mark;KNOBELOCH, John M.;DE DIOS MAGANA, Alfonso;DE PRADO GONZALEZ, Ana;FILADELFA DEL PRADO CATALINA, Miriam;GARCIA PAREDES, Maria Cristina;MARTIN DE LA NAVA, Eva Maria;MARTIN ORTEGA FINGER, Maria Dolores;MARTINEZ PEREZ, Jose Antonio;MATEO HERRANZ, Ana Isabel;PEREZ MARTINEZ, Carlos;SANCHEZ MARTINEZ, Concepcion US2010/160340, 2010, A1 Location in patent:Page/Page column 10