methyl 4-bromo-5-fluoro-2-methoxybenzoate

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl 4-bromo-2,5-difluorobenzoate (i-7c) (0.5 g, 2 mmol) in DMF (5 mL) at 0° C. was added NaOMe (25% in MeOH, 0.45 mL, 2 mmol). The reaction mixture was stirred at 0° C. for 10 min and then at rt for 30 min. The mixture was then brought back to 0° C. and quenched with EtOAc and 1M HCl. The organic layer was separated, and the aqueous phase was extracted with EtOAc, dried over Na2SO4, concentrated and purified by flash chromatography (Pentane/EtOAc=9:1) to give the title compound. LCMS (ESI) calc'd for C9H8BrFO3 [M+H]+: 263. found: 263 at rt for 30 min was then brought back to 0° C. quenched with EtOAc and 1M HCl The organic layer was separated the aqueous phase was extracted with EtOAc dried over Na2SO4 concentrated purified by flash chromatography (Pentane/EtOAc=9:1)

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

Procedure: Preparation according to Preparation 7, using boron tribromide (1.0 M, 25.0 ml, 25.2 mmol) in DCM (25 ml) and methyl 4-bromo-5-fluoro-2-methoxybenzoate (2.2 g, 8.4 mmol) in DCM (15 ml). Yield: 2.1 g. MS m/z (rel. intensity, 70 eV) 250 (M+, 40), 248 (M+, 41), 218 (99), 216 (bp), 188 (41), 186 (41), 81 (39). Preparation according to Preparation 7

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of methyl 4-bromo-2,5-difluorobenzoate (1.0 g, 3.98 mmol) in dry DMF (10 ml) was cooled down to 0° C. Sodium methoxide (25% in MeOH, 0.91 ml, 3.98 mmol) was dried with activated molecular sieves and slowly added to the starting material. The reaction mixture was stirred at 0° C. for 10 min and then at ambient temperature for 30 min. The mixture was then brought back to 0° C. and quenched with EtOAc (50 ml) and aqueous HCl (1 M, 50 ml). The phases were separated and the aqueous phase was extracted with EtOAc (2×100 ml), dried (Na2SO4), filtered and evaporated to give an oil. The crude product was purified by flash column chromatography (isooctane/EtOAc 9:1) gave the title compound (0.81 g, 75%). MS m/z (rel. intensity, 70 eV) 264 (M+, 30), 262 (M+, 31), 233 (65), 231 (bp), 229 (41). slowly added to the starting material at ambient temperature for 30 min was then brought back to 0° C. quenched with EtOAc (50 ml) and aqueous HCl (1 M, 50 ml) The phases were separated the aqueous phase was extracted with EtOAc (2×100 ml) dried (Na2SO4) filtered evaporated to give an oil The crude product was purified by flash column chromatography (isooctane/EtOAc 9:1)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of methyl 4-bromo-2,5-difluorobenzoate (1.0 g, 3.98 mmol) in dry DMF (10 ml) was cooled down to 0° C. Sodium methoxide (25% in MeOH, 0.91 ml, 3.98 mmol) was dried with activated molecular sieves and slowly added to the starting material. The reaction mixture was stirred at 0° C. for 10 min and then at ambient temperature for 30 min. The mixture was then brought back to 0° C. and quenched with EtOAc (50 ml) and aqueous HCl (1 M, 50 ml). The phases were separated and the aqueous phase was extracted with EtOAc (2×100 ml), dried (Na2SO4), filtered and evaporated to give an oil. The crude product was purified by flash column chromatography (isooctane/EtOAc 9:1) gave the title compound (0.81 g, 75%). MS m/z (rel. intensity, 70 eV) 264 (M+, 30), 262 (M+, 31), 233 (65), 231 (bp), 229 (41). slowly added to the starting material at ambient temperature for 30 min was then brought back to 0° C. quenched with EtOAc (50 ml) and aqueous HCl (1 M, 50 ml) The phases were separated the aqueous phase was extracted with EtOAc (2×100 ml) dried (Na2SO4) filtered evaporated to give an oil The crude product was purified by flash column chromatography (isooctane/EtOAc 9:1)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of methyl 4-bromo-2,5-difluorobenzoate (i-7c) (0.5 g, 2 mmol) in DMF (5 mL) at 0° C. was added NaOMe (25% in MeOH, 0.45 mL, 2 mmol). The reaction mixture was stirred at 0° C. for 10 min and then at rt for 30 min. The mixture was then brought back to 0° C. and quenched with EtOAc and 1M HCl. The organic layer was separated, and the aqueous phase was extracted with EtOAc, dried over Na2SO4, concentrated and purified by flash chromatography (Pentane/EtOAc=9:1) to give the title compound. LCMS (ESI) calc'd for C9H8BrFO3 [M+H]+: 263. found: 263 at rt for 30 min was then brought back to 0° C. quenched with EtOAc and 1M HCl The organic layer was separated the aqueous phase was extracted with EtOAc dried over Na2SO4 concentrated purified by flash chromatography (Pentane/EtOAc=9:1)

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

Procedure: Preparation according to Preparation 7, using boron tribromide (1.0 M, 25.0 ml, 25.2 mmol) in DCM (25 ml) and methyl 4-bromo-5-fluoro-2-methoxybenzoate (2.2 g, 8.4 mmol) in DCM (15 ml). Yield: 2.1 g. MS m/z (rel. intensity, 70 eV) 250 (M+, 40), 248 (M+, 41), 218 (99), 216 (bp), 188 (41), 186 (41), 81 (39). Preparation according to Preparation 7

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A solution of methyl 4-bromo-2,5-difluorobenzoate (1.0 g, 3.98 mmol) in dry DMF (10 ml) was cooled down to 0° C. Sodium methoxide (25% in MeOH, 0.91 ml, 3.98 mmol) was dried with activated molecular sieves and slowly added to the starting material. The reaction mixture was stirred at 0° C. for 10 min and then at ambient temperature for 30 min. The mixture was then brought back to 0° C. and quenched with EtOAc (50 ml) and aqueous HCl (1 M, 50 ml). The phases were separated and the aqueous phase was extracted with EtOAc (2×100 ml), dried (Na2SO4), filtered and evaporated to give an oil. The crude product was purified by flash column chromatography (isooctane/EtOAc 9:1) gave the title compound (0.81 g, 75%). MS m/z (rel. intensity, 70 eV) 264 (M+, 30), 262 (M+, 31), 233 (65), 231 (bp), 229 (41). slowly added to the starting material at ambient temperature for 30 min was then brought back to 0° C. quenched with EtOAc (50 ml) and aqueous HCl (1 M, 50 ml) The phases were separated the aqueous phase was extracted with EtOAc (2×100 ml) dried (Na2SO4) filtered evaporated to give an oil The crude product was purified by flash column chromatography (isooctane/EtOAc 9:1)