1: 2(R)-(3-chloro-4-methanesulfonylphenyl)-3-((S)-3-oxo-cyclopentyl)propionic acid With oxalyl dichloride; N,N-dimethyl-formamide in dichloromethane; toluene 1 h; Nitrogen atmosphere; 2: 2-amino-pyrazine With pyridine in dichloromethane T=25°C; 18 h;

pyridine in dichloromethane T=-16 - -5°C; 1.86667 h; Product distribution / selectivity;

1: (2R)-2-(3-chloro-4-methanesulfonylphenyl)-3-[(1R)-3-oxocyclopentyl]propanoic acid With oxalyl dichloride; N,N-dimethyl-formamide in dichloromethane; toluene T=25°C; 1 h; Inert atmosphere; 2: 2-amino-pyrazine With pyridine in tetrahydrofuran; dichloromethane T=-10 - 25°C; 18 h; Inert atmosphere; diastereoselective reaction;

1.1: AlCl3, aluminium chloride / chloroform / 0.5 h / 0 °C / |Inert atmosphere 1.2: 4 h / 0 - 20 °C / |Inert atmosphere 2.1: sodium hydroxide; water / toluene / 1.5 h / 50 - 60 °C / |Inert atmosphere 3.1: hydrazine hydrate; potassium hydroxide / 16 h / -50 - 100 °C / |Inert atmosphere 4.1: potassium carbonate; pivaloyl chloride / acetone / 0.33 h / -10 - 20 °C / |Inert atmosphere 5.1: lithium hexamethyldisilazane; n-butyllithium / hexane; tetrahydrofuran / 0.5 h / -15 - -7 °C / |Inert atmosphere 5.2: 3 h / -15 - 0 °C / |Inert atmosphere 6.1: sulfuric acid / water; 1,4-dioxane / 18 h / |Inert atmosphere; |Reflux 7.1: 3,3-dimethyldioxirane / acetone / 1 h / 25 °C / |Inert atmosphere 8.1: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane; toluene / 1 h / 25 °C / |Inert atmosphere 8.2: 18 h / -10 - 25 °C / |Inert atmosphere View Scheme

1.1: pyridinium p-toluenesulfonate / cyclohexane / 4 h / |Reflux; |Inert atmosphere; |Dean-Stark 2.1: diethylzinc / 1,2-dichloro-ethane / 0.42 h / -7 - 0 °C / |Inert atmosphere; |Enzymatic reaction 2.2: 2.5 h / -12 - 25 °C / |Inert atmosphere 3.1: potassium carbonate; trimethylsilyl iodide / dichloromethane / 1 h / -8 - -6 °C / |Inert atmosphere 4.1: lithium hexamethyldisilazane; n-butyllithium / hexane; tetrahydrofuran / 0.5 h / -15 - -7 °C / |Inert atmosphere 4.2: 3 h / -15 - 0 °C / |Inert atmosphere 5.1: sulfuric acid / water; 1,4-dioxane / 18 h / |Inert atmosphere; |Reflux 6.1: 3,3-dimethyldioxirane / acetone / 1 h / 25 °C / |Inert atmosphere 7.1: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane; toluene / 1 h / 25 °C / |Inert atmosphere 7.2: 18 h / -10 - 25 °C / |Inert atmosphere View Scheme

1.1: sodium hydroxide; water / toluene / 1.5 h / 50 - 60 °C / |Inert atmosphere 2.1: hydrazine hydrate; potassium hydroxide / 16 h / -50 - 100 °C / |Inert atmosphere 3.1: potassium carbonate; pivaloyl chloride / acetone / 0.33 h / -10 - 20 °C / |Inert atmosphere 4.1: lithium hexamethyldisilazane; n-butyllithium / hexane; tetrahydrofuran / 0.5 h / -15 - -7 °C / |Inert atmosphere 4.2: 3 h / -15 - 0 °C / |Inert atmosphere 5.1: sulfuric acid / water; 1,4-dioxane / 18 h / |Inert atmosphere; |Reflux 6.1: 3,3-dimethyldioxirane / acetone / 1 h / 25 °C / |Inert atmosphere 7.1: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane; toluene / 1 h / 25 °C / |Inert atmosphere 7.2: 18 h / -10 - 25 °C / |Inert atmosphere View Scheme

1.1: diethylzinc / 1,2-dichloro-ethane / 0.42 h / -7 - 0 °C / |Inert atmosphere; |Enzymatic reaction 1.2: 2.5 h / -12 - 25 °C / |Inert atmosphere 2.1: potassium carbonate; trimethylsilyl iodide / dichloromethane / 1 h / -8 - -6 °C / |Inert atmosphere 3.1: lithium hexamethyldisilazane; n-butyllithium / hexane; tetrahydrofuran / 0.5 h / -15 - -7 °C / |Inert atmosphere 3.2: 3 h / -15 - 0 °C / |Inert atmosphere 4.1: sulfuric acid / water; 1,4-dioxane / 18 h / |Inert atmosphere; |Reflux 5.1: 3,3-dimethyldioxirane / acetone / 1 h / 25 °C / |Inert atmosphere 6.1: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane; toluene / 1 h / 25 °C / |Inert atmosphere 6.2: 18 h / -10 - 25 °C / |Inert atmosphere View Scheme

1.1: potassium carbonate; trimethylsilyl iodide / dichloromethane / 1 h / -8 - -6 °C / |Inert atmosphere 2.1: lithium hexamethyldisilazane; n-butyllithium / hexane; tetrahydrofuran / 0.5 h / -15 - -7 °C / |Inert atmosphere 2.2: 3 h / -15 - 0 °C / |Inert atmosphere 3.1: sulfuric acid / water; 1,4-dioxane / 18 h / |Inert atmosphere; |Reflux 4.1: 3,3-dimethyldioxirane / acetone / 1 h / 25 °C / |Inert atmosphere 5.1: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane; toluene / 1 h / 25 °C / |Inert atmosphere 5.2: 18 h / -10 - 25 °C / |Inert atmosphere View Scheme

1.1: potassium carbonate; pivaloyl chloride / acetone / 0.33 h / -10 - 20 °C / |Inert atmosphere 2.1: lithium hexamethyldisilazane; n-butyllithium / hexane; tetrahydrofuran / 0.5 h / -15 - -7 °C / |Inert atmosphere 2.2: 3 h / -15 - 0 °C / |Inert atmosphere 3.1: sulfuric acid / water; 1,4-dioxane / 18 h / |Inert atmosphere; |Reflux 4.1: 3,3-dimethyldioxirane / acetone / 1 h / 25 °C / |Inert atmosphere 5.1: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane; toluene / 1 h / 25 °C / |Inert atmosphere 5.2: 18 h / -10 - 25 °C / |Inert atmosphere View Scheme

1.1: lithium hexamethyldisilazane; n-butyllithium / hexane; tetrahydrofuran / 0.5 h / -15 - -7 °C / |Inert atmosphere 1.2: 3 h / -15 - 0 °C / |Inert atmosphere 2.1: sulfuric acid / water; 1,4-dioxane / 18 h / |Inert atmosphere; |Reflux 3.1: 3,3-dimethyldioxirane / acetone / 1 h / 25 °C / |Inert atmosphere 4.1: N,N-dimethyl-formamide; oxalyl dichloride / dichloromethane; toluene / 1 h / 25 °C / |Inert atmosphere 4.2: 18 h / -10 - 25 °C / |Inert atmosphere View Scheme