Multi-step reaction with 10 steps
1.1: titanium(IV) tetraethanolate / tetrahydrofuran / 2 h / 18 - 25 °C
2.1: TurboGrignard / tetrahydrofuran / 2 h / -15 °C
2.2: -15 °C
3.1: potassium phosphate / tris-(dibenzylideneacetone)dipalladium(0); dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane / toluene; water / 5 h / 100 °C
4.1: dichloromethane / 1 h / 18 - 25 °C
5.1: caesium carbonate / ruphos; chloro-(2-dicyclohexylphosphino-2’,6’-diisopropoxy-1,1‘-biphenyl)[2-(2-aminoethyl)phenyl] palladium(ll) methyl-tert-butyl ether adduct / ethanol / 1.5 h / 110 °C
6.1: Chiralpak AD column Column / ethanol; carbon dioxide / Resolution of diastereomers
7.1: water; lithium hydroxide / tetrahydrofuran; methanol / 40 °C
7.2: 0 °C / pH ~ 2
8.1: dmap; N-ethyl-N,N-diisopropylamine; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride / dichloromethane / 0.17 h / 18 - 25 °C / Inert atmosphere
8.2: 18 - 25 °C
9.1: hydrogenchloride / 1,4-dioxane; methanol / 2 h / 18 - 25 °C
9.2: 0.17 h
10.1: N-ethyl-N,N-diisopropylamine; HATU / N,N-dimethyl-formamide / 1 h / 18 - 25 °C
With
hydrogenchloride; dmap; titanium(IV) tetraethanolate; potassium phosphate; TurboGrignard; water; caesium carbonate; 1-ethyl-(3-(3-dimethylamino)propyl)-carbodiimide hydrochloride; N-ethyl-N,N-diisopropylamine; HATU; lithium hydroxide;
dicyclohexyl-(2',6'-dimethoxybiphenyl-2-yl)-phosphane; tris-(dibenzylideneacetone)dipalladium(0); chloro-(2-dicyclohexylphosphino-2’,6’-diisopropoxy-1,1‘-biphenyl)[2-(2-aminoethyl)phenyl] palladium(ll) methyl-tert-butyl ether adduct; ruphos;
In
tetrahydrofuran; 1,4-dioxane; methanol; ethanol; dichloromethane; carbon dioxide; water; N,N-dimethyl-formamide; toluene;