3-(Methylthio)propyl (Methanesulfonate)

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of tert-butyl (3-{cyclopropyl[3-hydroxy-5-(3-methoxypropyl)benzyl](cyclopropyl)amino}-2-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]benzyl}-3-oxopropyl)carbamate from Example 70, Step 2 (1 eq.) in DMF (0.05 M) was added 3-(methylthio)propyl methanesulfonate from the previous step (1.4 eq.) and cesium carbonate (1.4 eq.). The resulting suspension was heated at 60° C. for 12 h. The reaction mixture was quenched sat. aq. NaHCO3 and then extracted with ether. The combined organic extracts were washed with water and brine, dried over MgSO4, filtered and the filtrate concentrated in vacuo. Purification of the crude product thus obtained by way of flash chromatography (SiO2, 3:2 (v/v) Hex:EtOAc→2:3 (v/v) Hex:EtOAc) afforded the title compound as a colorless oil. The reaction mixture was quenched sat. aq. NaHCO3 extracted with ether The combined organic extracts were washed with water and brine dried over MgSO4 filtered the filtrate concentrated in vacuo Purification of the crude product thus obtained by way of flash chromatography (SiO2, 3:2 (v/v)

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of tert-butyl (3-{cyclopropyl[3-hydroxy-5-(3-methoxypropyl)benzyl](cyclopropyl)amino}-2-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]benzyl}-3-oxopropyl)carbamate from Example 70, Step 2 (1 eq.) in DMF (0.05 M) was added 3-(methylthio)propyl methanesulfonate from the previous step (1.4 eq.) and cesium carbonate (1.4 eq.). The resulting suspension was heated at 60° C. for 12 h. The reaction mixture was quenched sat. aq. NaHCO3 and then extracted with ether. The combined organic extracts were washed with water and brine, dried over MgSO4, filtered and the filtrate concentrated in vacuo. Purification of the crude product thus obtained by way of flash chromatography (SiO2, 3:2 (v/v) Hex:EtOAc→2:3 (v/v) Hex:EtOAc) afforded the title compound as a colorless oil. The reaction mixture was quenched sat. aq. NaHCO3 extracted with ether The combined organic extracts were washed with water and brine dried over MgSO4 filtered the filtrate concentrated in vacuo Purification of the crude product thus obtained by way of flash chromatography (SiO2, 3:2 (v/v)

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-(methylthio)propan-1-ol in dichloromethane (0.2 M) was added sequentially at −78° C. Hunig's base (1.3 eq.) and methanesulfonyl chloride (1.3 eq.). The resulting reaction mixture was stirred at −78° C. for 1 h and then warmed slowly to RT. The reaction was quenched with sat. aq. NH4Cl and then extracted with ether. The combined organic extracts were washed with water and brine, dried over MgSO4, and filtered. Concentrated of the filtrate in vacuo afforded the title compound as a yellow oil. The resulting reaction mixture warmed slowly to RT The reaction was quenched with sat. aq. NH4Cl extracted with ether The combined organic extracts were washed with water and brine dried over MgSO4 filtered Concentrated of the filtrate in vacuo

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of tert-butyl (3-{cyclopropyl[3-hydroxy-5-(3-methoxypropyl)benzyl](cyclopropyl)amino}-2-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]benzyl}-3-oxopropyl)carbamate from Example 70, Step 2 (1 eq.) in DMF (0.05 M) was added 3-(methylthio)propyl methanesulfonate from the previous step (1.4 eq.) and cesium carbonate (1.4 eq.). The resulting suspension was heated at 60° C. for 12 h. The reaction mixture was quenched sat. aq. NaHCO3 and then extracted with ether. The combined organic extracts were washed with water and brine, dried over MgSO4, filtered and the filtrate concentrated in vacuo. Purification of the crude product thus obtained by way of flash chromatography (SiO2, 3:2 (v/v) Hex:EtOAc→2:3 (v/v) Hex:EtOAc) afforded the title compound as a colorless oil. The reaction mixture was quenched sat. aq. NaHCO3 extracted with ether The combined organic extracts were washed with water and brine dried over MgSO4 filtered the filtrate concentrated in vacuo Purification of the crude product thus obtained by way of flash chromatography (SiO2, 3:2 (v/v)

反応条件: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 3-(methylthio)propan-1-ol in dichloromethane (0.2 M) was added sequentially at −78° C. Hunig's base (1.3 eq.) and methanesulfonyl chloride (1.3 eq.). The resulting reaction mixture was stirred at −78° C. for 1 h and then warmed slowly to RT. The reaction was quenched with sat. aq. NH4Cl and then extracted with ether. The combined organic extracts were washed with water and brine, dried over MgSO4, and filtered. Concentrated of the filtrate in vacuo afforded the title compound as a yellow oil. The resulting reaction mixture warmed slowly to RT The reaction was quenched with sat. aq. NH4Cl extracted with ether The combined organic extracts were washed with water and brine dried over MgSO4 filtered Concentrated of the filtrate in vacuo