methyl 2-fluoro-6-formylbenzoate

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: This step was performed in five separate batches. For each batch, a solution of methyl 2-fluoro-6-formylbenzoate (3 g, 16.5 mmol), 2-benzamidoacetic acid (3.6, 20 mmol) and sodium acetate (1.62 g, 19.7 mmol) in acetic anhydride (30 mL) was heated at 100° C. in a microwave reactor (100 W, 150 psi) under nitrogen atmosphere for 2 hours. The reaction mixtures were diluted with EtOAc (100 mL) and washed with saturated aqueous Na2CO3. The combined organic layers were concentrated in vacuo to give the title compound as a brown solid, which was used without further purification (15 g). ESI-MS m/z [M+H]+ 326.2. separate batches The reaction mixtures washed with saturated aqueous Na2CO3 The combined organic layers were concentrated in vacuo

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Into a solution of methyl 2-fluoro-6-vinylbenzoate (31 g, 0.172 mol) in dry dichloromethane (300 mL) was bubbled O3 at −78° C. over a 30 minute period. Next, nitrogen gas was bubbled into the solution until it turned colorless. Dimethylsulfane (84.13 g, 1.36 mol) was added dropwise to the solution, which was subsequently warmed to RT and stirred for 2 hours. The mixture was then washed with water (30 mL) and extracted with DCM (3×300 mL). The combined organic layers were dried over Na2SO4 and concentrated. The crude product was purified by column chromatography eluting with a gradient of EtOAc (10-100%) and PE to give the title compound (21 g, 67%). 1H NMR (400 MHz, CDCl3) δ ppm 10.01 (s, 1H), 7.65-7.63 (d, J=7.6 Hz, 1H), 7.56-7.53 (dd, J1=5.2 Hz, J2=8.0 Hz, 1H), 7.35-7.30 (t, J=8.4 Hz, 1H), 3.94 (s, 3H). Next, nitrogen gas was bubbled into the solution until it The mixture was then washed with water (30 mL) extracted with DCM (3×300 mL) The combined organic layers were dried over Na2SO4 concentrated The crude product was purified by column chromatography eluting with a gradient of EtOAc (10-100%) and PE