Multi-step reaction with 7 steps
1.1: pig liver esterase, 36290 U; sodium hydroxide / methanol; water / 63 h / -10 °C / pH 7 / aq. phosphate buffer; Inert atmosphere; Enzymatic reaction
1.2: 8 - 40 °C / Inert atmosphere
2.1: lithium hydroxide / water / 0 - 20 °C / Inert atmosphere
3.1: lithium borohydride / tetrahydrofuran / 5 h / Inert atmosphere; Reflux
3.2: 20 °C / Reflux; Inert atmosphere
4.1: lithium diisopropyl amide / tetrahydrofuran; hexane / 1 h / -78 °C / Inert atmosphere
4.2: 3 h / -78 °C / Inert atmosphere
5.1: ruthenium trichloride; hydrogen; (+)-(R)-[2,3,2',3'-tetrahydro-5,5'-bi(1,4-benzodioxin)-6,6'-diyl]bis(diphenylphosphane) / ethanol / 24 h / 80 °C / 7500.75 Torr / Autoclave
6.1: dmap; triethylamine / dichloromethane / 5 h / Inert atmosphere
7.1: 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; lithium diisopropyl amide / tetrahydrofuran; hexane / -78 - -40 °C / Inert atmosphere
7.2: -78 - 0 °C / Inert atmosphere
With
dmap; 1,3-dimethyl-3,4,5,6-tetrahydro-2(1H)-pyrimidinone; ruthenium trichloride; lithium borohydride; pig liver esterase, 36290 U; hydrogen; triethylamine; sodium hydroxide; lithium hydroxide; lithium diisopropyl amide; (+)-(R)-[2,3,2',3'-tetrahydro-5,5'-bi(1,4-benzodioxin)-6,6'-diyl]bis(diphenylphosphane);
In
tetrahydrofuran; methanol; ethanol; hexane; dichloromethane; water;
4.2: Claisen condensation / 7.1: Frater-Seebach alkylation / 7.2: Frater-Seebach alkylation;
DOI:10.1002/anie.201106117