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    • 24. 发明申请
    • Process for the Preparation of Enantiomerically Pure 1-Substituted-3-Aminoalcohols
    • 对映异构纯的1-取代的3-氨基醇的制备方法
    • US20090156833A1
    • 2009-06-18
    • US11884542
    • 2006-02-14
    • Walter BriedenMartin ClausenJohn McGarrityHanspeter MettlerColette MettlerDominique Michel
    • Walter BriedenMartin ClausenJohn McGarrityHanspeter MettlerColette MettlerDominique Michel
    • C07D333/36
    • C07C303/22C07B2200/07C07C213/02C07C221/00C07C309/04C07C309/07C07C309/30C07C215/30C07C225/16
    • A process for the preparation of N-monosubstituted β-aminoalcohol sulfonates of formula (Ia), (Ib): wherein R1 is C6-20-aryl or C4-12-heteroaryl, each optionally being substituted with one or more halogen atoms and/or one or more C1-4-alkyl or C1-4-alkoxy groups, R2 is C1-4-alkyl or C6-20-aryl, each aryl optionally being substituted with one or more halogen atoms and/or one or more C1-4-alkyl or C1-4-alkoxy groups and wherein R3 is selected from the group consisting of C1-18-alkyl, C6-20-cycloalkyl, C6-20-aryl and C7-20-aralkyl residues. The process has the steps of (a) reacting a methyl ketone, a primary amine, formaldehyde and a sulfonic acid, at a pressure above 1.5 bar, optionally in a organic solvent, the organic solvent optionally containing water, to afford N-monosubstituted β-aminoketone sulfonates of formula (II): wherein R1, R2 and R3 are as defined above, and (b) asymmetrically hydrogenating. The sulfonates in the presence of a base and a catalyst of a transition metal and a disphosphine ligand, in a polar solvent, optionally in the presence of water.
    • 制备式(Ia),(Ib)的N-单取代的β-氨基醇磺酸盐的方法:其中R1是C6-20-芳基或C4-12 - 杂芳基,每个任选被一个或多个卤素原子和/ 或一个或多个C 1-4 - 烷基或C 1-4 - 烷氧基,R 2是C 1-4 - 烷基或C 6-20 - 芳基,每个芳基任选地被一个或多个卤素原子和/或一个或多个C 1〜 4-烷基或C 1-4 - 烷氧基,并且其中R 3选自C 1-18 - 烷基,C 6-20 - 环烷基,C 6-20 - 芳基和C 7-20 - 芳烷基残基。 该方法具有以下步骤:(a)使甲基酮,伯胺,甲醛和磺酸在高于1.5巴的压力下,任选地在有机溶剂(任选含有水的有机溶剂)中反应,得到N-单取代的β (II)的氨基酮磺酸盐:其中R1,R2和R3如上定义,和(b)不对称氢化。 在极性溶剂中,任选地在水存在下,在过渡金属和二膦配体的碱存在下和催化剂存在下的磺酸盐。