DIMETHYL 3-BROMOPHTHALATE

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a stirred solution of 3-Bromophthalic acid dimethyl ester (0.82 g, 3.0 mmol) in toluene (20 mL), were added S-BINAP (56 mg, 0.09 mmol), Pd2(dba)3 (55 mg, 0.06 mmol), Cs2CO3 (1.37 g, 4.2 mmol), and 1-methoxy-2-propanamine (0.32 g, 3.6 mmol), and the resulting mixture was heated to reflux with stirring under nitrogen for 24 hours. The mixture was allowed to cool to room temperature, and diethyl ether was added (70 mL). The mixture was filtered, and the filtrate was evaporated in vacuo. The residue was chromatographed eluting with 17:3 hexanes-ethyl acetate. The resulting material was further purified by preparative HPLC, eluting with 11:9 water-acetonitrile, and providing 0.32 g of the product in 38% yield: 1H NMR (DMSO-d6) δ1.14 (d, J=6.4 Hz, 3H), 3.29 (s, 3H), 3.37 (d, J=4.8 Hz, 2H), 3.74 (s, 3H), 3.77 (s, 3H), 3.74-3.80 (m, 1H), 6.53 (d, J=7.8 Hz, 1H), 6.76 (d, J=7.3 Hz, 1H), 6.99 (d, J=8.6 Hz, 1H), 7.38 (t, J=7.8 Hz, 1H). the resulting mixture was heated to reflux The mixture was filtered the filtrate was evaporated in vacuo The residue was chromatographed eluting with 17:3 hexanes-ethyl acetate The resulting material was further purified by preparative HPLC eluting with 11:9 water-acetonitrile

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 3-bromophthalic acid (2.5 g, 10 mmol) in DMF (20 mL), were added iodomethane (3.1 g, 22 mmol) and sodium bicarbonate (1.8 g, 22 mmol). The mixture was heated to 70° C. with stirring for 26 hours. The solvent was evaporated in vacuo, and the residue was partitioned between diethyl ether (100 mL) and water (100 mL). The organic phase was washed with sat. sodium bicarbonate (100 mL) and brine (100 mL), and dried (MgSO4). The solvent was evaporated in vacuo, and dried under high vacuum to afford 2.4 g (86%) of the product as a white solid: 1H NMR (DMSO-d6) δ 3.84 (s, 3H), 3.86 (s, 3H), 7.57 (t, J=8.0 Hz, 1H), 8.01 (d, J=8.1 Hz, 2H). The solvent was evaporated in vacuo the residue was partitioned between diethyl ether (100 mL) and water (100 mL) The organic phase was washed with sat. sodium bicarbonate (100 mL) and brine (100 mL) dried (MgSO4) The solvent was evaporated in vacuo dried under high vacuum

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 3-bromophthalic acid (2.5 g, 10 mmol) in DMF (20 mL), were added iodomethane (3.1 g, 22 mmol) and sodium bicarbonate (1.8 g, 22 mmol). The mixture was heated to 70° C. with stirring for 26 hours. The solvent was evaporated in vacuo, and the residue was partitioned between diethyl ether (100 mL) and water (100 mL). The organic phase was washed with sat. sodium bicarbonate (100 mL) and brine (100 mL), and dried (MgSO4). The solvent was evaporated in vacuo, and dried under high vacuum to afford 2.4 g (86%) of the product as a white solid: 1H NMR (DMSO-d6) δ 3.84 (s, 3H), 3.86 (s, 3H), 7.57 (t, J=8.0 Hz, 1H), 8.01 (d, J=8.1 Hz, 2H). The solvent was evaporated in vacuo the residue was partitioned between diethyl ether (100 mL) and water (100 mL) The organic phase was washed with sat. sodium bicarbonate (100 mL) and brine (100 mL) dried (MgSO4) The solvent was evaporated in vacuo dried under high vacuum

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: To a stirred solution of 3-Bromophthalic acid dimethyl ester (0.82 g, 3.0 mmol) in toluene (20 mL), were added S-BINAP (56 mg, 0.09 mmol), Pd2(dba)3 (55 mg, 0.06 mmol), Cs2CO3 (1.37 g, 4.2 mmol), and 1-methoxy-2-propanamine (0.32 g, 3.6 mmol), and the resulting mixture was heated to reflux with stirring under nitrogen for 24 hours. The mixture was allowed to cool to room temperature, and diethyl ether was added (70 mL). The mixture was filtered, and the filtrate was evaporated in vacuo. The residue was chromatographed eluting with 17:3 hexanes-ethyl acetate. The resulting material was further purified by preparative HPLC, eluting with 11:9 water-acetonitrile, and providing 0.32 g of the product in 38% yield: 1H NMR (DMSO-d6) δ1.14 (d, J=6.4 Hz, 3H), 3.29 (s, 3H), 3.37 (d, J=4.8 Hz, 2H), 3.74 (s, 3H), 3.77 (s, 3H), 3.74-3.80 (m, 1H), 6.53 (d, J=7.8 Hz, 1H), 6.76 (d, J=7.3 Hz, 1H), 6.99 (d, J=8.6 Hz, 1H), 7.38 (t, J=7.8 Hz, 1H). the resulting mixture was heated to reflux The mixture was filtered the filtrate was evaporated in vacuo The residue was chromatographed eluting with 17:3 hexanes-ethyl acetate The resulting material was further purified by preparative HPLC eluting with 11:9 water-acetonitrile

Conditions: temp:70.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of 3-bromophthalic acid (2.5 g, 10 mmol) in DMF (20 mL), were added iodomethane (3.1 g, 22 mmol) and sodium bicarbonate (1.8 g, 22 mmol). The mixture was heated to 70° C. with stirring for 26 hours. The solvent was evaporated in vacuo, and the residue was partitioned between diethyl ether (100 mL) and water (100 mL). The organic phase was washed with sat. sodium bicarbonate (100 mL) and brine (100 mL), and dried (MgSO4). The solvent was evaporated in vacuo, and dried under high vacuum to afford 2.4 g (86%) of the product as a white solid: 1H NMR (DMSO-d6) δ 3.84 (s, 3H), 3.86 (s, 3H), 7.57 (t, J=8.0 Hz, 1H), 8.01 (d, J=8.1 Hz, 2H). The solvent was evaporated in vacuo the residue was partitioned between diethyl ether (100 mL) and water (100 mL) The organic phase was washed with sat. sodium bicarbonate (100 mL) and brine (100 mL) dried (MgSO4) The solvent was evaporated in vacuo dried under high vacuum