4-bromo-2-methoxybenzonitrile

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

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

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

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

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

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

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

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

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-bromo-2-methoxybenzonitrile (0.424 g, 2.000 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)nicotinaldehyde (0.466 g, 2.000 mmol), tetrakis(triphenylphosphine)palladium(0) (0.058 g, 0.050 mmol) and sodium carbonate (2M in water, 2.00 mL, 4.00 mmol) in DME (50 mL) was heated to 90° C. for 6 h. After filtration through a pad of dry Na2SO4 and concentration, the residue was purified by column and yielded a colorless solid (430 mg). 1H NMR (400 MHz, CDCl3): δ 4.04 (s, 3H), 6.99 (s, 1H), 7.27 (d, J=4.7 Hz, 1H), 7.71 (d, J=7.9 Hz, 1H), 8.34 (t, J=2 Hz, 1H), 9.07 (d, J=2.36 Hz, 1H), 9.12 (d, J=1.9 Hz, 1H), 10.22 (s, 1H). After filtration through a pad of dry Na2SO4 and concentration the residue was purified by column

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

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 3-necked 1 L round-bottomed flask was equipped with an overhead stirrer, and a nitrogen line. The flask was charged with 45.56 g (215 mmol) of 4-bromo-2-methoxybenzonitrile, 64 mL (277 mmol) of tri-isopropylborate and 500 mL of THF. The solution was cooled to −78° C. in a dry-ice/acetone bath. n-Butyllithium (2.5M, 110 mL, 275 mmol) was added dropwise via addition funnel. The mixture was stirred for 30 minutes and 2N HCl was added. The mixture was stirred for an hour and poured into water. The mixture was extracted with Et2O. The organic solution was backextracted with 1N NaOH. The aqueous layer was washed with Et2O and acidified with conc. HCl. The mixture was extracted with Et2O. The organic extract was dried (MgSO4) and evaporated in vacuo to afford 20.77 g (55%) of the product as a white solid. 1H NMR (500 MHz, d6-DMSO) δ 7.68 (d, 1H), 7.59 (s, 1H), 7.47 (d, 1H), 3.95 (s, 3H). A 3-necked 1 L round-bottomed flask was equipped with an overhead stirrer The mixture was stirred for an hour The mixture was extracted with Et2O The aqueous layer was washed with Et2O The mixture was extracted with Et2O The organic extract was dried (MgSO4) evaporated in vacuo

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A 3-necked 1 L round-bottomed flask was equipped with an overhead stirrer, and a nitrogen line. The flask was charged with 45.56 g (215 mmol) of 4-bromo-2-methoxybenzonitrile, 64 mL (277 mmol) of tri-isopropylborate and 500 mL of THF. The solution was cooled to −78° C. in a dry-ice/acetone bath. n-Butyllithium (2.5M, 110 mL, 275 mmol) was added dropwise via addition funnel. The mixture was stirred for 30 minutes and 2N HCl was added. The mixture was stirred for an hour and poured into water. The mixture was extracted with Et2O. The organic solution was backextracted with 1N NaOH. The aqueous layer was washed with Et2O and acidified with conc. HCl. The mixture was extracted with Et2O. The organic extract was dried (MgSO4) and evaporated in vacuo to afford 20.77 g (55%) of the product as a white solid. 1H NMR (500 MHz, d6-DMSO) δ 7.68 (d, 1H), 7.59 (s, 1H), 7.47 (d, 1H), 3.95 (s, 3H). A 3-necked 1 L round-bottomed flask was equipped with an overhead stirrer The mixture was stirred for an hour The mixture was extracted with Et2O The aqueous layer was washed with Et2O The mixture was extracted with Et2O The organic extract was dried (MgSO4) evaporated in vacuo