2-O-[(Z)-1-aminoethylideneamino] 1-O-methyl 3-fluorobenzene-1,2-dicarboxylate → 3-Fluoro-2-(3-methyl-1,2,4-oxadiazol-5-yl)benzoic acid

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Reaction Conditions

Reaction Steps

To THF (15 mL) was added 2 M i-PrMgCl in THF (2.2 mL, 4.47 mmol). This mixture was cooled to −78° C. and the product of Step B (1.09 g, 3.58 mmol) was added dropwise in THF (20 mL). The mixture was stirred for 30 min at −78° C. and then CO2 from a lecture bottle was bubbled into the solution for 3 h while allowing the temperature to slowly rise. When the temperature reached −20° C. the dry ice bath was replaced with an ice bath, bubbling of CO2 was ceased and the mixture was allowed to come to room temperature overnight. The mixture was quenched by the addition of H2O and a small amount of Et2O. The organic layer was washed 2× with 2 N NaOH and the combined aqueous layers were then washed 3× with Et2O. The aqueous layer was then acidified with concentrated HCl and extracted with DCM. The combined organic layers were dried over Na2SO4, filtered and concentrated in vacuo to afford the desired product as a white solid (661 mg, 83%). MS (ESI) mass calculated for C10H7FN2O3, 222.04; m/z found, 223.0. 1H NMR (500 MHz, CDCl3): 7.96 (d, J=7.8, 1H), 7.72-7.64 (m, 1H), 7.50-7.44 (m, 1H), 2.56-2.48 (m, 3H).

Provenance & Evidence