tert-butyl 3-bromobutanoate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-{2-[4-(2,6-Dichloro-benzyloxy)-phenyl]-morpholin-4-yl}-butyric acid tert-butyl ester was obtained according to a similar manner. The required 3-bromobutyric acid tert-butyl ester was prepared as follows: To a solution of 3-bromobutyric acid (5.0 mL; 47.0 mmol) in tetrahydrofuran (50 mL) was added dropwise trifluoroacetic anhydride (13.7 mL; 98.7 mmol) at −40° C. After 1 hour at −40° C. tert-butyl alcohol (20 mL) was added. The resulting mixture was allowed to warm to RT and stirred overnight. Subsequently, the reaction mixture was concentrated in vacuo. The residue was treated with 2M aqueous NaOH solution and extracted with Et2O. The organic layer was dried (Na2SO4), and concentrated in vacuo to afford 3-bromobutyric acid tert-butyl ester (6.05 g), which was used as such. The required 3-bromobutyric acid tert-butyl ester was prepared Subsequently, the reaction mixture was concentrated in vacuo The residue was treated with 2M aqueous NaOH solution extracted with Et2O The organic layer was dried (Na2SO4) concentrated in vacuo

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-(4-octyloxy-phenyl)-morpholine (0.24 gram, 1.1 mmol), 3-bromobutyric acid tert-butyl ester (0.24 g; 1.1 mmol), sodium iodide (27.4 mg; 0.2 mmol), and DBU (0.4 mL; 2.7 mmol) in CH3CN (10 mL) was heated in a closed vessel at 120° C. After cooling to RT the reaction mixture was partitioned between 5% aqueous NaHCO3 solution and EtOAc. The layers were separated and the organic layer was dried (Na2SO4), filtered, and concentrated. The residue was purified by column chromatography (SiO2, Et2O) to afford 3-[2-(4-octyloxy-phenyl)-morpholin-4-yl]-butyric acid tert-butyl ester (0.15 g). After cooling to RT the reaction mixture was partitioned between 5% aqueous NaHCO3 solution and EtOAc The layers were separated the organic layer was dried (Na2SO4) filtered concentrated The residue was purified by column chromatography (SiO2, Et2O)

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-(4-octyloxy-phenyl)-morpholine (0.24 gram, 1.1 mmol), 3-bromobutyric acid tert-butyl ester (0.24 g; 1.1 mmol), sodium iodide (27.4 mg; 0.2 mmol), and DBU (0.4 mL; 2.7 mmol) in CH3CN (10 mL) was heated in a closed vessel at 120° C. After cooling to RT the reaction mixture was partitioned between 5% aqueous NaHCO3 solution and EtOAc. The layers were separated and the organic layer was dried (Na2SO4), filtered, and concentrated. The residue was purified by column chromatography (SiO2, Et2O) to afford 3-[2-(4-octyloxy-phenyl)-morpholin-4-yl]-butyric acid tert-butyl ester (0.15 g). After cooling to RT the reaction mixture was partitioned between 5% aqueous NaHCO3 solution and EtOAc The layers were separated the organic layer was dried (Na2SO4) filtered concentrated The residue was purified by column chromatography (SiO2, Et2O)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Prepared as for Ex. 2, starting with tert-butyl 3-bromo-butyrate and N-[2-(2,6-bis-hydroxymethyl-pyridin-4-yloxy)-ethyl]-2-nitro-benzenesulfonamide: Prepared as for Ex

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: The required 3-bromobutyric acid tert-butyl ester was prepared as follows: To a solution of 3-bromobutyric acid (5.0 mL; 47.0 mmol) in tetrahydrofuran (50 mL) was added dropwise trifluoroacetic anhydride (13.7 mL; 98.7 mmol) at −40° C. After 1 hour at −40° C. tert-butyl alcohol (20 mL) was added. The resulting mixture was allowed to warm to RT and stirred overnight. Subsequently, the reaction mixture was concentrated in vacuo. The residue was treated with 2M aqueous NaOH solution and extracted with Et2O. The organic layer was dried (Na2SO4), and concentrated in vacuo to afford 3-bromobutyric acid tert-butyl ester (6.05 g), which was used as such. The required 3-bromobutyric acid tert-butyl ester was prepared Subsequently, the reaction mixture was concentrated in vacuo The residue was treated with 2M aqueous NaOH solution extracted with Et2O The organic layer was dried (Na2SO4) concentrated in vacuo

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-(4-octyloxy-phenyl)-morpholine (0.24 gram, 1.1 mmol), 3-bromobutyric acid tert-butyl ester (0.24 g; 1.1 mmol), sodium iodide (27.4 mg; 0.2 mmol), and DBU (0.4 mL; 2.7 mmol) in CH3CN (10 mL) was heated in a closed vessel at 120° C. After cooling to RT the reaction mixture was partitioned between 5% aqueous NaHCO3 solution and EtOAc. The layers were separated and the organic layer was dried (Na2SO4), filtered, and concentrated. The residue was purified by column chromatography (SiO2, Et2O) to afford 3-[2-(4-octyloxy-phenyl)-morpholin-4-yl]-butyric acid tert-butyl ester (0.15 g). After cooling to RT the reaction mixture was partitioned between 5% aqueous NaHCO3 solution and EtOAc The layers were separated the organic layer was dried (Na2SO4) filtered concentrated The residue was purified by column chromatography (SiO2, Et2O)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-{2-[4-(2,6-Dichloro-benzyloxy)-phenyl]-morpholin-4-yl}-butyric acid tert-butyl ester was obtained according to a similar manner. The required 3-bromobutyric acid tert-butyl ester was prepared as follows: To a solution of 3-bromobutyric acid (5.0 mL; 47.0 mmol) in tetrahydrofuran (50 mL) was added dropwise trifluoroacetic anhydride (13.7 mL; 98.7 mmol) at −40° C. After 1 hour at −40° C. tert-butyl alcohol (20 mL) was added. The resulting mixture was allowed to warm to RT and stirred overnight. Subsequently, the reaction mixture was concentrated in vacuo. The residue was treated with 2M aqueous NaOH solution and extracted with Et2O. The organic layer was dried (Na2SO4), and concentrated in vacuo to afford 3-bromobutyric acid tert-butyl ester (6.05 g), which was used as such. The required 3-bromobutyric acid tert-butyl ester was prepared Subsequently, the reaction mixture was concentrated in vacuo The residue was treated with 2M aqueous NaOH solution extracted with Et2O The organic layer was dried (Na2SO4) concentrated in vacuo

Conditions: temp:120.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 2-(4-octyloxy-phenyl)-morpholine (0.24 gram, 1.1 mmol), 3-bromobutyric acid tert-butyl ester (0.24 g; 1.1 mmol), sodium iodide (27.4 mg; 0.2 mmol), and DBU (0.4 mL; 2.7 mmol) in CH3CN (10 mL) was heated in a closed vessel at 120° C. After cooling to RT the reaction mixture was partitioned between 5% aqueous NaHCO3 solution and EtOAc. The layers were separated and the organic layer was dried (Na2SO4), filtered, and concentrated. The residue was purified by column chromatography (SiO2, Et2O) to afford 3-[2-(4-octyloxy-phenyl)-morpholin-4-yl]-butyric acid tert-butyl ester (0.15 g). After cooling to RT the reaction mixture was partitioned between 5% aqueous NaHCO3 solution and EtOAc The layers were separated the organic layer was dried (Na2SO4) filtered concentrated The residue was purified by column chromatography (SiO2, Et2O)