(-)4[4-(二甲胺基)-1-(4-氟苯基)-1-(羟基丁基)-3-(羟基 甲基)氰苯.氢溴酸盐合成路线 （共 17 条）
反应条件
1: With D-di-4-methylbenzoyl tartaric acid in isopropyl alcohol T=20°C; 12 h; Resolution of racemate; 2: With sodium hydroxide in water; toluene
参考文献
Hangzhou Minsheng Pharm. Co., Ltd.
Patent: EP1700851 A1, 2006 ;
Location in patent: Page/Page column 9 ;
反应条件
1: With hydrogenchloride; potassium dihydrogenphosphate; water in methanol; water T=20 - 25°C; pH=6 - 8.5; Resolution of racemate; 2: With hydrogenchloride in methanol; water T=20 - 25°C; pH=6; 3: Resolution of racemate;
参考文献
Cotticelli, Giovanni; Rocchietti, Silvia; Terreni, Marco; Pregnolato, Massimo; Salvetti, Raul
Patent: US2007/238887 A1, 2007 ;
Location in patent: Page/Page column 3-4 ;
反应条件
lipoprotein lipase pseudomonas sp. in 1,4-dioxane T=50°C; 504 h;
参考文献
H. LUNDBECK A/S
Patent: WO2005/77891 A1, 2005 ;
Location in patent: Page/Page column 27-28 ;
反应条件
enzyme Lipozyme TL IM; vinyl butanoate in toluene T=40°C; 16 h; Product distribution / selectivity;
参考文献
H. LUNDBECK A/S
Patent: WO2004/14821 A1, 2004 ;
Location in patent: Page 55 ;
反应条件
in tetrahydrofuran; toluene T=-60°C; 0.25 h; Product distribution / selectivity;
参考文献
SANDOZ AG
Patent: WO2007/82771 A1, 2007 ;
Location in patent: Page/Page column 23-24 ;
反应条件
ammonia; water in methanol 4 h; Resolution of racemate; Product distribution / selectivity;
参考文献
Cotticelli, Giovanni; Rocchietti, Silvia; Terreni, Marco; Pregnolato, Massimo; Salvetti, Raul
Patent: US2007/238887 A1, 2007 ;
Location in patent: Page/Page column 4 ;
反应条件
1: 4-(4-fluorobenzoyl)-3-(hydroxymethyl)benzonitrile With methyl boronic acid in toluene T=20 - 70°C; 0.75 h; 2: 3-(N,N-dimethylamino)-propylmagnesium chloride in tetrahydrofuran; toluene T=-60°C; 0.2 h; Product distribution / selectivity;
参考文献
SANDOZ AG
Patent: WO2007/82771 A1, 2007 ;
Location in patent: Page/Page column 23 ;
反应条件
1: 4-(4-fluorobenzoyl)-3-(hydroxymethyl)benzonitrile With (1S,2R)-(+)-N-methylephedrine in toluene T=20 - 70°C; 0.75 h; 2: 3-(N,N-dimethylamino)-propylmagnesium chloride in tetrahydrofuran; toluene T=-80°C; 0.2 h; Product distribution / selectivity;
参考文献
SANDOZ AG
Patent: WO2007/82771 A1, 2007 ;
Location in patent: Page/Page column 21 ;
反应条件
1: 3-(N,N-dimethylamino)-propylmagnesium chloride; C27H28BFN2O3 in tetrahydrofuran; water; toluene T=-40 - -35°C; 0.666667 - 0.833333 h; 2: With sulfuric acid in tetrahydrofuran; water; toluene pH=~ 2; 0.0833333 h; 3: 2,2,2-trimethylacetic acid With ammonia Product distribution / selectivity; more than 3 stages;
参考文献
SANDOZ AG
Patent: WO2007/82771 A1, 2007 ;
Location in patent: Page/Page column 24-25 ;
反应条件
1: 4-(4-fluorobenzoyl)-3-(hydroxymethyl)benzonitrile With (1S,2R)-(+)-N-methylephedrine in toluene T=20 - 70°C; 0.75 h; 2: 3-(N,N-dimethylamino)-propylmagnesium chloride in tetrahydrofuran; toluene T=-80°C; 0.2 h; Product distribution / selectivity;
参考文献
SANDOZ AG
Patent: WO2007/82771 A1, 2007 ;
Location in patent: Page/Page column 21 ;
