METHOD FOR PREPARING NITROOXY-DERIVATIVES OF NAPROXEN Russian patent published in 2008 - IPC C07C201/02 C07C203/04 

FIELD: organic chemistry, chemical technology.

SUBSTANCE: invention relates to a method for synthesis of nitrooxy-derivatives of naproxen. Invention describes a method for synthesis of compound of the general formula (A)

wherein R means compound of the formula: wherein R' means hydrogen atom or bromine (Br) atom; R₁-R₁₂ are similar or different and mean independently hydrogen atom, linear or branched (C₁-C₆)-alkyl optionally substituted with aryl; each among m, n, o, p, q, r and s means independently a whole number from 0 to 6; p = 0 or 1; X means oxygen atom (O), sulfur (S) atom, -SO_, -SO₂, -NR₁₃ or -PR₁₃ wherein R₁₃ means hydrogen atom, (C₁-C₆)-alkyl; or X is chosen from group including: -cycloalkylene with 5-7 carbon atoms in cycloalkylene ring wherein ring is optionally substituted with side chains T wherein T means linear or branched alkyl with 1-10 carbon atoms; -arylene optionally substituted with one or more halogen atoms, linear or branched alkyl groups comprising from 1 to 4 carbon atoms, or linear or branched (C₁-C₃)-perfluoroalkyl; -5 or 6-membered saturated, unsaturated or aromatic heterocyclic ring chosen from formula X1-X13:

. Indicated method involves: (i) adding reaction of compound of the formula (B): R-COOZ wherein R is given above; Z means hydrogen atom or cation chosen from Li⁺, Na⁺, Ca⁺⁺, Mg⁺⁺, tetraalkyl ammonium, tetraalkyl phosphonium with compound of the following formula (C):

wherein R₁-R₂ and m, n, o, p, q, r and s are given above; Y is chosen from halogen atom, -BF₄, -SbF₆, FSO_3-, R_ASO_3- wherein R_A means linear or branched (C₁-C₆)-alkyl optionally substituted with one or more halogen atoms, or (C₁-C₆)-alkylaryl; -R_BCOO^- wherein R_B means linear or branched (C₁-C₆)-alkyl, aryl optionally substituted with one or more halogen atoms or NO₂-groups, (C₄-C₁₀)-heteroaryl and comprising one or more heteroatoms that are similar or different and chosen from nitrogen, oxygen, sulfur or phosphorus atoms; -aryloxy-group optionally substituted with one or more halogen atoms or NO₂-groups, or heteroaryloxy-group, and (ii) conversion if necessary compound of the formula (A) wherein R' means Br atom to compound of the formula (A) wherein R' means hydrogen atom.

EFFECT: improved method of synthesis.

9 cl, 4 ex