(5R)-4-(5-氯-1,3-苯并恶唑-2-基)-5-甲基-1,4-二氮杂环庚烷-1-鎓 (2S,3S)-2,3-二(苯甲酰氧基)丁二酸盐合成路线 （共 7 条）
反应条件
1: in tetrahydrofuran T=20°C; 4.91667 h; Resolution of racemate; 2: With isopropanol acetate in methanol T=20°C; 22.25 h; Resolution of racemate; optical yield given as percent ee;
参考文献
Baxter, Carl A.; Cleator, Ed; Brands, Karel M. J.; Edwards, John S.; Reamer, Robert A.; Sheen, Faye J.; Stewart, Gavin W.; Strotman, Neil A.; Wallace, Debra J.
Organic Process Research and Development, 2011 , vol. 15, # 2 p. 367 - 375
反应条件
1.1: dichloromethane; N,N-dimethyl-formamide / 1.75 h / 20 - 25 °C 2.1: triethylamine / dichloromethane / 2.5 h / 0 - 20 °C 3.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / dichloromethane; water; acetonitrile / 10.08 h / 20 - 40 °C 4.1: tetrahydrofuran / 5 - 60 °C 5.1: sodium acetate; sodium tris(acetoxy)borohydride; acetic acid / dichloromethane / 15 - 20 °C 6.1: tetrahydrofuran / 4.92 h / 20 °C / Resolution of racemate 6.2: 22.25 h / 20 °C / Resolution of racemate View Scheme
参考文献
MERCK SHARP and DOHME CORP.; MERCK SHARP and DOHME LIMITED; BAXTER, Carl, A.; CLEATOR, Edward; KRSKA, Shane, W.; SHEEN, Faye; STEWART, Gavin; STROTMAN, Neil; WALLACE, Debra, J.; WRIGHT, Timothy
Patent: WO2012/148553 A1, 2012 ;
WO 2012/148553 A1
反应条件
1.1: methanol; water / 2 h / 0 - 20 °C 2.1: dichloromethane; N,N-dimethyl-formamide / 1.75 h / 20 - 25 °C 3.1: triethylamine / dichloromethane / 2.5 h / 0 - 20 °C 4.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / dichloromethane; water; acetonitrile / 10.08 h / 20 - 40 °C 5.1: tetrahydrofuran / 5 - 60 °C 6.1: sodium acetate; sodium tris(acetoxy)borohydride; acetic acid / dichloromethane / 15 - 20 °C 7.1: tetrahydrofuran / 4.92 h / 20 °C / Resolution of racemate 7.2: 22.25 h / 20 °C / Resolution of racemate View Scheme
参考文献
MERCK SHARP and DOHME CORP.; MERCK SHARP and DOHME LIMITED; BAXTER, Carl, A.; CLEATOR, Edward; KRSKA, Shane, W.; SHEEN, Faye; STEWART, Gavin; STROTMAN, Neil; WALLACE, Debra, J.; WRIGHT, Timothy
Patent: WO2012/148553 A1, 2012 ;
WO 2012/148553 A1
反应条件
1.1: tetrahydrofuran / 5 - 60 °C 2.1: sodium acetate; sodium tris(acetoxy)borohydride; acetic acid / dichloromethane / 15 - 20 °C 3.1: tetrahydrofuran / 4.92 h / 20 °C / Resolution of racemate 3.2: 22.25 h / 20 °C / Resolution of racemate View Scheme
参考文献
MERCK SHARP and DOHME CORP.; MERCK SHARP and DOHME LIMITED; BAXTER, Carl, A.; CLEATOR, Edward; KRSKA, Shane, W.; SHEEN, Faye; STEWART, Gavin; STROTMAN, Neil; WALLACE, Debra, J.; WRIGHT, Timothy
Patent: WO2012/148553 A1, 2012 ;
WO 2012/148553 A1
反应条件
1.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / dichloromethane; water; acetonitrile / 10.08 h / 20 - 40 °C 2.1: tetrahydrofuran / 5 - 60 °C 3.1: sodium acetate; sodium tris(acetoxy)borohydride; acetic acid / dichloromethane / 15 - 20 °C 4.1: tetrahydrofuran / 4.92 h / 20 °C / Resolution of racemate 4.2: 22.25 h / 20 °C / Resolution of racemate View Scheme
参考文献
Baxter, Carl A.; Cleator, Ed; Brands, Karel M. J.; Edwards, John S.; Reamer, Robert A.; Sheen, Faye J.; Stewart, Gavin W.; Strotman, Neil A.; Wallace, Debra J.
Organic Process Research and Development, 2011 , vol. 15, # 2 p. 367 - 375
反应条件
1.1: triethylamine / dichloromethane / 2.5 h / 0 - 20 °C 2.1: 1,8-diazabicyclo[5.4.0]undec-7-ene / dichloromethane; water; acetonitrile / 10.08 h / 20 - 40 °C 3.1: tetrahydrofuran / 5 - 60 °C 4.1: sodium acetate; sodium tris(acetoxy)borohydride; acetic acid / dichloromethane / 15 - 20 °C 5.1: tetrahydrofuran / 4.92 h / 20 °C / Resolution of racemate 5.2: 22.25 h / 20 °C / Resolution of racemate View Scheme
参考文献
Baxter, Carl A.; Cleator, Ed; Brands, Karel M. J.; Edwards, John S.; Reamer, Robert A.; Sheen, Faye J.; Stewart, Gavin W.; Strotman, Neil A.; Wallace, Debra J.
Organic Process Research and Development, 2011 , vol. 15, # 2 p. 367 - 375
反应条件
1: C13H16ClN3O*C18H14O8 With sodium hydroxide in dichloromethane; water T=20°C; 1 h; 2: 2-(2H-1,2,3-triazol-2-yl)-5-methylbenzoic acid With oxalyl dichloride in dichloromethane; N,N-dimethyl-formamide T=0 - 10°C; 1 h; 3: (R)-5-chloro-2-(5-methyl-[1,4]diazepan-1-yl)benzoxazole With triethylamine in dichloromethane; N,N-dimethyl-formamide T=0 - 15°C; 1 h; optical yield given as percent ee;
参考文献
Baxter, Carl A.; Cleator, Ed; Brands, Karel M. J.; Edwards, John S.; Reamer, Robert A.; Sheen, Faye J.; Stewart, Gavin W.; Strotman, Neil A.; Wallace, Debra J.
Organic Process Research and Development, 2011 , vol. 15, # 2 p. 367 - 375
