Ethyl Acetate → Methyl 4-(4-fluorophenyl)-2-isopropyl-8-methanesulfonyl-5,6,7,8-tetrahydro-[1,8]naphthyridine-3-carboxylate

Participants

Reaction Steps

A solution of (MeSO2)2O (15.9 g, 0.091 mol) in anhydrous CH2Cl2 (50 mL) was added to a solution of Part C methyl 4-(4-fluorophenyl)-2-isopropyl-5,6,7,8-tetrahydro-[1,8]naphthyridine-3-carboxylate (10. g, 0.030 mol) and 3,5-lutidine (20.9 mL, 0.182 mol) in anhydrous toluene (100 mL) at room temperature. The reaction mixture was stirred at room temperature for 3 days. Ethyl acetate (200 mL) and H2O (50 mL) were added, and the resulting two phases were separated. The organic phase was washed with aqueous NaHCO3 (5%, 50 mL), followed by half-saturated brine (50 mL). The solvent was removed under reduced pressure to afford a yellowish oil which solidified slowly. The crude material was recrystallized from i-PrOH/H2O (85:15, 45 mL) to afford 10.5 g (85% yield) of methyl 4-(4-fluorophenyl)-2-isopropyl-8-methanesulfonyl-5,6,7,8-tetrahydro-[1,8]naphthyridine-3-carboxylate as a off-white solid.

Provenance & Evidence