Ataluren synthesis

9synthesis methods

Product Name:Ataluren
CAS Number:775304-57-9
Molecular formula:C15H9FN2O3
Molecular Weight:284.24

The sequence to construct ataluren, which was described by the authors at PTC Therapeutics, commenced with commercially available methyl 3-cyanobenzoate (38). This ester was exposed to hydroxylamine in aqueous tert-butanol and warmed gently until the reaction was deemed complete. Then this mixture was treated with 2-fluorobenzoyl chloride dropwise and subsequently triethylamine dropwise. To minimize exotherm and undesired side products, careful control of the addition of reagents was achieved through slow dropwise addition of these liquid reagents. Upon complete consumption of starting materials and formation of amidooxime 39, the aqueous reaction mixture was then heated to 85 ℃ to facilitate 1,2,4-oxadiazole formation, resulting in the tricyclic ester 40 in excellent yield across the three steps. Finally, saponification of ester 40 through the use of sodium hydroxide followed by acidic quench gave ataluren (V) in 96% over the two-step sequence.

5-(2-fluorophenyl)-3-(3-methylphenyl)-1,2,4-oxadiazole

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Yield:775304-57-9 85%

Reaction Conditions:

with basic cobalt(II) carbonate;sodium bromide in acetic acid at 95; for 11 h;Green chemistry;

Steps:

Oxidation of 4 and 3 methyl-5-R-1,2,4-oxadiazoles (general procedure).

General procedure: Oxidation process was carried out in an ideal mixing reactor. A starting methylarene 1a-h (13 mmol), cobalt acetate (1.3 mmol), and sodium bromide (1.3 mmol) were dissolved in glacial acetic acid (40 mL). Then, the solution was heated to 95 °C and air was fed to the reactor. The reaction mixture was allowed to stand for 11 h at 95 °C and cooled to ~20 °C, a precipitate formed was filtered.

References:

Krasouskaya;Danilova;Baikov;Kolobov;Kofanov [Russian Chemical Bulletin,2015,vol. 64,# 1,p. 142 - 145][Izv. Akad. Nauk, Ser. Khim.,2015,# 1,p. 142 - 145,4]

393-52-2 Synthesis