Multi-step reaction with 12 steps
1.1: Candita antarctica lipase B / hexane / 3 h / 20 °C / Inert atmosphere; Resolution of racemate; Enzymatic reaction
2.1: water; sodium hydroxide / methanol / 4 h / Reflux
3.1: triphenylphosphine; di-isopropyl azodicarboxylate / tetrahydrofuran / 2 h / 0 °C / Inert atmosphere
4.1: water; sodium hydroxide / methanol / 1 h / Reflux
5.1: methyllithium / tetrahydrofuran / 0.67 h / -20 - 20 °C / Inert atmosphere
5.2: 1 h / 40 °C / Inert atmosphere
5.3: 0.25 h / 0 °C / Inert atmosphere
6.1: tert.-butyl lithium / diethyl ether; pentane / 0.17 h / -78 °C / Inert atmosphere
6.2: 2 h / -78 - 20 °C / Inert atmosphere
6.3: 2 h / 20 °C / Darkness
7.1: pyridine / dichloromethane / 1 h / 0 °C / Inert atmosphere
8.1: tetra-N-butylammonium tribromide / methanol / 4 h / 20 °C / Inert atmosphere
9.1: hydrogen; [Ir(cod)(SIMes)(Pyr)]+PF6- / dichloromethane / 18 h / 20 °C / 67506.8 Torr / Autoclave
10.1: 1H-imidazole; dmap / dichloromethane / 0.5 h / 20 °C / Inert atmosphere
11.1: potassium carbonate / methanol / 6 h / 60 °C / Inert atmosphere
12.1: 2,6-dimethylpyridine / dichloromethane / 5 h / 0 °C / Inert atmosphere
With
pyridine; 1H-imidazole; 2,6-dimethylpyridine; dmap; di-isopropyl azodicarboxylate; Candita antarctica lipase B; [Ir(cod)(SIMes)(Pyr)]+PF6-; water; methyllithium; hydrogen; tert.-butyl lithium; tetra-N-butylammonium tribromide; potassium carbonate; triphenylphosphine; sodium hydroxide;
In
tetrahydrofuran; methanol; diethyl ether; hexane; dichloromethane; pentane;
DOI:10.1002/anie.201303776