Ammonium Chloride → 1-Tert-butyl 3-methyl 3-(5-chloropyridin-2-yl)azetidine-1,3-dicarboxylate

Participants

Reaction Conditions

Reaction Steps

To a solution of 5-chloro-2-fluoropyridine (0.5 g, 3.8 mmol, Eq: 1.00) and 1-tert-butyl 3-methyl azetidine-1,3-dicarboxylate (818 mg, 3.8 mmol, Eq: 1.00) in toluene (5 ml) was added dropwise at 0° C. for 15 min a 0.5 M solution of KHMDS (7.6 ml, 3.8 mmol, Eq: 1.00) in toluene. The colorless solution turned into yellow-orange. After stirring at 0° C. for 45 min, the reaction mixture was allowed to warm to 20° C. and stirred for 2.5 h. A saturated aqueous NH4Cl solution (50 ml) was added and the aqueous phase was extracted with AcOEt (2×75 ml). The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude material was purified by flash chromatography (silica gel, 12 g, 10% to 60% AcOEt in heptane) to yield a colorless gum (0.234 g; 19%). m/z=327.2 [M+H]+.

Provenance & Evidence