2-[(2-methylphenyl)methyl]piperidine

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-methyl-2-(5-trifluoromethanesulfonyloxy-4′-trifluoromethyl-biphenyl-3-yl)-pentanoic acid ethyl ester (1g) (190 mg, 0.37 mmol) in toluene (2.5 mL) in a sealed tube was added racemic-2-(di-t-butylphosphino)-1,1′-binaphthyl (44 mg, 0.11 mmol), Pd(OAc)2 (83 mg, 0.37 mmol), 2-(2-methyl-benzyl)-piperidine (98 mg, 0.52 mmol). The system was flushed with nitrogen. To this was added NaOtBu (53 mg, 0.56 mmol) and heated to 100° C. for 1 h. The reaction was cooled to room temperature and quenched by slow addition of water. The mixture was extracted with EtOAc (3×20 mL). The organic phase was washed with saturated NaHCO3 solution and brine. The organic fraction was dried (MgSO4) and concentrated in vacuo. The crude mixture was purified by ISCO column chromatography to obtain 4-methyl-2-{5-[2-(2-methyl-benzyl)-piperidin-1-yl]-4′-trifluoromethyl-biphenyl-3-yl}-pentanoic acid ethyl ester. Calcd for C34H40F3NO2 (M+H) 552.68, Found 552.41. The system was flushed with nitrogen The reaction was cooled to room temperature quenched by slow addition of water The mixture was extracted with EtOAc (3×20 mL) The organic phase was washed with saturated NaHCO3 solution and brine The organic fraction was dried (MgSO4) concentrated in vacuo The crude mixture was purified by ISCO column chromatography

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 4-methyl-2-(5-trifluoromethanesulfonyloxy-4′-trifluoromethyl-biphenyl-3-yl)-pentanoic acid ethyl ester (1g) (190 mg, 0.37 mmol) in toluene (2.5 mL) in a sealed tube was added racemic-2-(di-t-butylphosphino)-1,1′-binaphthyl (44 mg, 0.11 mmol), Pd(OAc)2 (83 mg, 0.37 mmol), 2-(2-methyl-benzyl)-piperidine (98 mg, 0.52 mmol). The system was flushed with nitrogen. To this was added NaOtBu (53 mg, 0.56 mmol) and heated to 100° C. for 1 h. The reaction was cooled to room temperature and quenched by slow addition of water. The mixture was extracted with EtOAc (3×20 mL). The organic phase was washed with saturated NaHCO3 solution and brine. The organic fraction was dried (MgSO4) and concentrated in vacuo. The crude mixture was purified by ISCO column chromatography to obtain 4-methyl-2-{5-[2-(2-methyl-benzyl)-piperidin-1-yl]-4′-trifluoromethyl-biphenyl-3-yl}-pentanoic acid ethyl ester. Calcd for C34H40F3NO2 (M+H) 552.68, Found 552.41. The system was flushed with nitrogen The reaction was cooled to room temperature quenched by slow addition of water The mixture was extracted with EtOAc (3×20 mL) The organic phase was washed with saturated NaHCO3 solution and brine The organic fraction was dried (MgSO4) concentrated in vacuo The crude mixture was purified by ISCO column chromatography