2-chloroethoxycyclopropane

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of trans-tert-butyl 3-({cyclopropyl[3-hydroxy-5-(3-methoxypropyl)benzyl]amino}carbonyl)-4-(1-methyl-2-oxo-1,2-dihydro-4-pyridinyl)-1-piperidinecarboxylate (1.0 eq., Example 92) in DMF (0.1 M) was added cesium carbonate (2 eq.), sodium iodide (0.05 eq.) and (2-chloroethoxy)cyclopropane (3 eq.). The reaction mixture was heated at 100° C. for 22 h. After cooling to RT, the reaction was quenched with sat. aq. ammonium chloride and extracted with EtOAc. The combined organic extracts were washed further 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, 95:5 (v/v) CH2Cl2:MeOH) afforded the title compound as a colorless oil. After cooling to RT the reaction was quenched with sat. aq. ammonium chloride extracted with EtOAc The combined organic extracts were washed further 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, 95:5 (v/v) CH2Cl2:MeOH)

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of tert-butyl (3R,4S)-3-({cyclopropyl[3-hydroxy-5-(3-methoxy-propyl)benzyl]-amino}carbonyl)-4-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]-phenyl}piperidine-1-carboxylate (1 eq.) from Example 1/Step 2 in DMF (0.1 M) was added (2-chloroethoxy)cyclopropane (3 eq.) and cesium carbonate (2 eq.). The reaction was heated to 100° C. and stirred for 3 h. After cooling to rt, the reaction was diluted with ether. The organic extract was washed with water, brine, dried over MgSO4, and concentrated in vacuo. The crude product was purified by flash column chromatography (SiO2, 35% EtOAc in Hex) to afford the title compound as an oil. After cooling to rt The organic extract was washed with water, brine dried over MgSO4 concentrated in vacuo The crude product was purified by flash column chromatography (SiO2, 35% EtOAc in Hex)

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of tert-butyl (3R,4S)-3-({cyclopropyl[3-hydroxy-5-(3-methoxy-propyl)benzyl]-amino}carbonyl)-4-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]-phenyl}piperidine-1-carboxylate (1 eq.) from Example 1/Step 2 in DMF (0.1 M) was added (2-chloroethoxy)cyclopropane (3 eq.) and cesium carbonate (2 eq.). The reaction was heated to 100° C. and stirred for 3 h. After cooling to rt, the reaction was diluted with ether. The organic extract was washed with water, brine, dried over MgSO4, and concentrated in vacuo. The crude product was purified by flash column chromatography (SiO2, 35% EtOAc in Hex) to afford the title compound as an oil. After cooling to rt The organic extract was washed with water, brine dried over MgSO4 concentrated in vacuo The crude product was purified by flash column chromatography (SiO2, 35% EtOAc in Hex)

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of trans-tert-butyl 3-({cyclopropyl[3-hydroxy-5-(3-methoxypropyl)benzyl]amino}carbonyl)-4-(1-methyl-2-oxo-1,2-dihydro-4-pyridinyl)-1-piperidinecarboxylate (1.0 eq., Example 92) in DMF (0.1 M) was added cesium carbonate (2 eq.), sodium iodide (0.05 eq.) and (2-chloroethoxy)cyclopropane (3 eq.). The reaction mixture was heated at 100° C. for 22 h. After cooling to RT, the reaction was quenched with sat. aq. ammonium chloride and extracted with EtOAc. The combined organic extracts were washed further 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, 95:5 (v/v) CH2Cl2:MeOH) afforded the title compound as a colorless oil. After cooling to RT the reaction was quenched with sat. aq. ammonium chloride extracted with EtOAc The combined organic extracts were washed further 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, 95:5 (v/v) CH2Cl2:MeOH)

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of trans-tert-butyl 3-({cyclopropyl[3-hydroxy-5-(3-methoxypropyl)benzyl]amino}carbonyl)-4-(1-methyl-2-oxo-1,2-dihydro-4-pyridinyl)-1-piperidinecarboxylate (1.0 eq., Example 92) in DMF (0.1 M) was added cesium carbonate (2 eq.), sodium iodide (0.05 eq.) and (2-chloroethoxy)cyclopropane (3 eq.). The reaction mixture was heated at 100° C. for 22 h. After cooling to RT, the reaction was quenched with sat. aq. ammonium chloride and extracted with EtOAc. The combined organic extracts were washed further 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, 95:5 (v/v) CH2Cl2:MeOH) afforded the title compound as a colorless oil. After cooling to RT the reaction was quenched with sat. aq. ammonium chloride extracted with EtOAc The combined organic extracts were washed further 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, 95:5 (v/v) CH2Cl2:MeOH)

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of tert-butyl (3R,4S)-3-({cyclopropyl[3-hydroxy-5-(3-methoxy-propyl)benzyl]-amino}carbonyl)-4-{4-[2-(2,6-dichloro-4-methylphenoxy)ethoxy]-phenyl}piperidine-1-carboxylate (1 eq.) from Example 1/Step 2 in DMF (0.1 M) was added (2-chloroethoxy)cyclopropane (3 eq.) and cesium carbonate (2 eq.). The reaction was heated to 100° C. and stirred for 3 h. After cooling to rt, the reaction was diluted with ether. The organic extract was washed with water, brine, dried over MgSO4, and concentrated in vacuo. The crude product was purified by flash column chromatography (SiO2, 35% EtOAc in Hex) to afford the title compound as an oil. After cooling to rt The organic extract was washed with water, brine dried over MgSO4 concentrated in vacuo The crude product was purified by flash column chromatography (SiO2, 35% EtOAc in Hex)

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of trans-tert-butyl 3-({cyclopropyl[3-hydroxy-5-(3-methoxypropyl)benzyl]amino}carbonyl)-4-(1-methyl-2-oxo-1,2-dihydro-4-pyridinyl)-1-piperidinecarboxylate (1.0 eq., Example 92) in DMF (0.1 M) was added cesium carbonate (2 eq.), sodium iodide (0.05 eq.) and (2-chloroethoxy)cyclopropane (3 eq.). The reaction mixture was heated at 100° C. for 22 h. After cooling to RT, the reaction was quenched with sat. aq. ammonium chloride and extracted with EtOAc. The combined organic extracts were washed further 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, 95:5 (v/v) CH2Cl2:MeOH) afforded the title compound as a colorless oil. After cooling to RT the reaction was quenched with sat. aq. ammonium chloride extracted with EtOAc The combined organic extracts were washed further 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, 95:5 (v/v) CH2Cl2:MeOH)