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    • 9. 发明授权
    • Process for the preparation of 2-trifluoromethyl-5-(1-substituted)alkylpyridines
    • 2-三氟甲基-5-(1-取代)烷基吡啶的制备方法
    • US08742125B2
    • 2014-06-03
    • US13303182
    • 2011-11-23
    • Gary Alan RothDouglas C. BlandJames R. McConnell
    • Gary Alan RothDouglas C. BlandJames R. McConnell
    • C07D213/00
    • C07D213/32
    • 2-Trifluoromethyl-5-(1-substituted)alkylpyridines of formula (I) wherein R1 and R2 independently represent H, C1-C4 alkyl, or either of R1 or R2 taken together with R3 represent a 4- to 6-membered saturated ring, or R1 taken together with R2 represents a 3- to 6-membered saturated ring optionally substituted with an O or a N atom, R3 represents C1-C4 alkyl or R3 taken together with either of R1 or R2 represent a 4- to 6-membered saturated ring, and X represents CH2, O or S, are produced efficiently and in high yield from an 4-alkoxy-1,1,1-trifluorobut-3-en-2-one (II) wherein R represents a C1-C4 alkyl by condensation with an enamine (III) wherein R1, R2, R3 and X are as previously defined, and R4 and R5 independently represent C1-C8 alkyl, C2-C8 alkenyl, C1-C8 arylalkyl, C1-C8 haloalkyl, C1-C8 alkoxyalkyl, C1-C8 alkylaminoalkyl, aryl or heteroaryl or R4 and R5 taken together with N represent a 5- or 6-membered saturated or unsaturated ring, to provide an intermediate of the formula (IV) wherein R1, R2, R3, R4, R5 and X are as previously defined followed by cyclization in the presence of ammonia or a reagent capable of generating ammonia. Both reactions are performed in the same nonpolar solvent without isolation and purification of intermediates.
    • 式(I)的2-三氟甲基-5-(1-取代的)烷基吡啶其中R 1和R 2独立地表示H,C 1 -C 4烷基,或者与R 3一起与R 3一起表示4至6元饱和环 或者R 1与R 2一起表示任选被O或N原子取代的3至6元饱和环,R 3表示C 1 -C 4烷基或与R 1或R 2中的任一个一起表示的4-至6-元饱和环, 通过4-烷氧基-1,1,1-三氟丁-3-烯-2-酮(II)有效且高产率地制备X代表CH 2,O或S的化合物,其中R代表C1- C4烷基,其中R1,R2,R3和X如前定义,并且R4和R5独立地表示C1-C8烷基,C2-C8链烯基,C1-C8芳基烷基,C1-C8卤代烷基,C1 -C 8烷氧基烷基,C 1 -C 8烷基氨基烷基,芳基或杂芳基或R 4和R 5与N一起表示5-或6-元饱和或不饱和环,以提供式(IV)的中间体 )其中R 1,R 2,R 3,R 4,R 5和X如前所定义,随后在氨或能产生氨的试剂存在下环化。 两种反应都是在相同的非极性溶剂中进行,而不需要分离和纯化中间体。