Methyl 2-amino-4,5-difluorobenzoate

Step 3 :; [0109] To a solution of methyl 4, 5-difluoro-2-nitrobenzoate Ib (23.0 g, 106 mmol) in EtOAc (200 mL), was added 10percent Pd/C (wet, 50 percent water, 6.0 g), and the mixture was shaken on a Parr hydrogenator at 50 PSI for 3 hr. The reaction mixture was then filtered through a celite pad and the filtrate was concentrated by rotary evaporation to yield methyl 2-amino-4, 5-difluorobenzoate Ic as a colorless solid, 19.Og (96percent).Procedure H: TMSCHProcedure H: TMSCHStep 3 :; [0109] To a solution of methyl 4, 5-difluoro-2-nitrobenzoate Ib (23.0 g, 106 mmol) in EtOAc (200 mL), was added 10percent Pd/C (wet, 50 percent water, 6.0 g), and the mixture was shaken on a Parr hydrogenator at 50 PSI for 3 hr. The reaction mixture was then filtered through a celite pad and the filtrate was concentrated by rotary evaporation to yield methyl 2-amino-4, 5-difluorobenzoate Ic as a colorless solid, 19.Og (96percent).Procedure H: TMSCHProcedure H: TMSCHTo a solution of 70-1 (1.00 g, 5.34 mmol, 1 eq) and 70-lc (1.50 g, 8.02 mmol, 1.5 eq) in DCM (15 mL) were added Cu(OAc)2 (1.40 g, 8.02 mmol, 1.5 eq) and DIEA (1.30 g, 10.69 mmol, 1.8 mL, 2 eq). The mixture was degassed, purged with 02 for 3 times and stirred at 20C for 16 hr. The mixture was concentrated. The residue was dissolved in EA (10 mL) and washed with H20 (3 mL *3). The combined organic layers were washed with brine (3 mL *3), dried over Na2S04, filtered and concentrated under reduced pressure. The residue was purified by flash silica gel chromatography to give 70-2 (650.0 mg, 1.96 mmol, 36.7% yield). 1H NMR (400 MHz, CDCl3) d 9.61 (br s, 1H), 7.79 (dd, 7 = 9.0, 11.1 Hz, 1H), 7.58 (d, J= 8.5 Hz, 2H), 7.25 (d, .7= 2.3 Hz, 1H), 7.10 (dd, 7= 6.9, 12.8 Hz, 1H), 3.92 - 3.88 (m, 3H)