methyl 6-amino-3-bromo-2-methoxybenzoate

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

Procedure: A solution of Example 385B (6.83 g, 25.2 mmol) in anhydrous methanol (300 mL) was refluxed for 48 hours. The solution was concentrated and the residue was purified by chromatography on a silica gel column eluting with 20% ethyl acetate/hexane to give the desired product 5.7 g, 87.2% yield. 1H NMR (DMSO-d6) δ 3.70 (s, 3H), 3.82 (s, 3H), 5.92 (s, 2H), 6.45 (d, 1H), 7.30 (d, 1H); MS (ESI(−)) m/e 258, 260 (M−H)−. The solution was concentrated the residue was purified by chromatography on a silica gel column eluting with 20% ethyl acetate/hexane

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

Procedure: A mixture of Example 470A (9.8 g, 50.7 mmol), DMF (50 mL), and dichloromethane (150 mL) was cooled to 0° C., treated portionwise with N-bromosuccinimide (12.6 g, 76 mmol), stirred until all the starting material was consumed, and filtered. The filter cake was washed with dichloromethane combined filtrates were concentrated, treated with anhydrous methanol (450 mL), and heated to reflux for 54 hours. Purification by flash column chromatography on silica gel with 15% ethyl acetate/hexanes provided the desired product. MS (ESI(+)) m/e 260, 262 (M+H)+, 277, 279 (M+NH4)+, 282, 284 (M+Na)+; (ESI(−)) m/e 258, 260 (M−H)−; 1H NMR (300 MHz, DMSO-d6) δ 7.34 (d, 1H), 6.50 (d, 1H), 5.63 (s, 2H), 3.82 (s, 3H), 3.71 (s, 3H). was consumed filtered The filter cake was washed with dichloromethane combined filtrates were concentrated treated with anhydrous methanol (450 mL) heated to reflux for 54 hours Purification by flash column chromatography on silica gel with 15% ethyl acetate/hexanes