Ammonium Chloride → 2-(5-Chloro-3-fluoro-pyridin-2-yl)-azetidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester

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To a solution of 5-chloro-2,3-difluoropyridine (1.39 g, 9.29 mmol, Eq: 1.00) and 1-tert-butyl 2-methyl azetidine-1,2-dicarboxylate (2 g, 9.29 mmol, Eq: 1.00) in toluene (15 ml) was added dropwise at 0° C. over 15 min a 0.5 M solution of KHMDS (18.6 ml, 9.29 mmol, Eq: 1.00) in toluene. The colorless solution turned into light brown. After stirring at 0° C. for 45 min, the reaction mixture was allowed to warm up to 25° C. The reaction mixture was stirred for 2.5 h. Saturated aqueous NH4Cl solution (100 ml) was added and the aqueous phase was extracted with AcOEt (2×150 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, 40 g, 10% to 60% AcOEt in heptane) to yield a colorless viscous oil as a racemate (1.746 g; 55%). m/z=345.2 [M+H]+.

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