Ammonium Chloride → 1,1-Dimethylethyl 3-(3,4-difluorophenyl)-3-hydroxy-1-azetidinecarboxylate

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Reaction Conditions

Reaction Steps

To a solution of 4-bromo-1,2-difluorobenzene (1.35 g, 7.01 mmol) in dry diethylether (50 ml) at −78° C. under nitrogen was added n-hexyllithium (2.3 M in hexane, 3.0 ml, 7.01 mmol) dropwise. The mixture was stirred for 10 min after which a solution of 1-Boc-azetidone (1.0 g, 5.85 mmol) in dry diethyl ether (10 mL) was added dropwise. The resulting mixture was stirred at −78° C. for 10 min and then brought to ambient temperature and stirred for 10 min. Saturated aqueous ammonium chloride (50 mL,) was added and the mixture was extracted with tert-butyl methyl ether (2×50 ml). The combined organic phase was dried (Na2SO4), filtered and evaporated to dryness. The crude product was purified by flash column chromatography on silica gel (ethylacetate/isooctane 1:1) to give the title compound (1.06 g). MS m/z (rel. intensity, 70 eV) 285 (M+, 1), 156 (60), 141 (43), 127 (80), 57 (bp).

Provenance & Evidence