Ammonium Chloride → 4-{4-[2-(2,6-Dichloro-4-methyl-phenoxy)-ethoxy]-phenyl}-5,6-dihydro-2H-pyridine-1,3-dicarboxylic Acid 1-tert-butyl Ester 3-methyl Ester

Participants

Reaction Conditions

Reaction Steps

1-[2-(4-Bromo-phenoxy)-ethoxy]-2,6-dichloro-4-methyl-benzene (16.6 g, 44.2 mmol) was dissolved in THF (150 mL), and the sol. was cooled to −78° C. BuLi (1.6M in hexane, 31.4 mL, 50.3 mmol) was added, and the mixture was stirred at −78° C. for 30 min. ZnCl2 (1M in THF, 56.0 mL, 56.0 mmol) was added, and the mixture was allowed to warm up to rt. The mixture was stirred at rt for 1 h. A sol. of 4-trifluoromethanesulfonyloxy-5,6-dihydro-2H-pyridine-1,3-dicarboxylic acid 1-tert-butyl ester 3-methyl ester (WO 2004/002957; 14.3 g, 36.7 mmol) in THF (30 mL), and then a sol. of Pd(PPh3)4 (1.23 g, 1.06 mmol) in THF (30 mL) were added. The mixture was stirred at 50° C. over 20 min, and cooled to 0° C. Aq. 10% NH4Cl was added. The mixture was extracted with EtOAc. The org. extracts were washed with aq. 10% NH4Cl, water, and brine. The org. layer was dried over MgSO4, filtered, and the solvents were removed under reduced pressure. Purification of the residue by FC (EtOAc/heptane 1:4→EtOAc) yielded the title compound (19.7 g, quantitative yield). LC-MS: tR=1.20 min; ES+: 536.77.

Provenance & Evidence