2-fluoro-6-iodobenzaldehyde

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:; See reaction.notes.procedure_details.

Procedure: 2-Fluoro-6-iodobenzonitrile (10.274 g) was dissolved in toluene (100 ml), followed by the dropwise addition of 1.5M diisobutyl aluminium hydride/toluene solution (31 ml) in nitrogen atmosphere at −70° C., and the mixture was stirred for 25 min. Subsequently, it was stirred at room temperature for further 45 min. To the mixture was added 5% sulfuric acid, and it was stirred for 1 hr. Sequentially, the resulting solution was extracted with ethyl acetate, and the resulting organic layer was washed with water, dried (over MgSO4) and evaporated. The resulting residue was purified by silica gel column chromatography (ethyl acetate/hexane system), to give the title compound as a yellow oil (8.683 g, yield; 83%). Subsequently, it was stirred at room temperature for further 45 min was stirred for 1 hr Sequentially, the resulting solution was extracted with ethyl acetate the resulting organic layer was washed with water dried (over MgSO4) evaporated The resulting residue was purified by silica gel column chromatography (ethyl acetate/hexane system)

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

Procedure: To a mixture of 2-iodo-6-fluorobenzaldehyde (45 mmol) in H2O (22.5 ml), EtOH (22.5 ml), and ice (20 g) was added hydroxylamine hydrochloride (3.19 g, 49.5 mmol, 1.1 eq.). Then, 112.5 mmol of 50% NaOH (4.5 g in 4.5 ml H2O, 2.5 eq.) was added with stirring. Enough ice to keep the temperature at 25-30° C. was added. The reaction was stirred for 2 h, acidified with conc. HCl to pH 4 (ice was added to keep the temperature at 25-30° C.), and extracted with Et2O. The combined organic solution was washed with brine, dried (MgSO4), filtered, and concentrated. The residue was chromatographed on silica gel using ethyl acetate in hexanes (5%-10%) to give 2-iodo-6-fluorobenzaldehyde oxime (7.06 g, 59% over 2 steps) as an oil that solidified over time. at 25-30° C. was added The reaction was stirred for 2 h was added at 25-30° C. extracted with Et2O The combined organic solution was washed with brine dried (MgSO4) filtered concentrated The residue was chromatographed on silica gel

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

Procedure: To a mixture of 2-iodo-6-fluorobenzaldehyde (45 mmol) in H2O (22.5 ml), EtOH (22.5 ml), and ice (20 g) was added hydroxylamine hydrochloride (3.19 g, 49.5 mmol, 1.1 eq.). Then, 112.5 mmol of 50% NaOH (4.5 g in 4.5 ml H2O, 2.5 eq.) was added with stirring. Enough ice to keep the temperature at 25-30° C. was added. The reaction was stirred for 2 h, acidified with conc. HCl to pH 4 (ice was added to keep the temperature at 25-30° C.), and extracted with Et2O. The combined organic solution was washed with brine, dried (MgSO4), filtered, and concentrated. The residue was chromatographed on silica gel using ethyl acetate in hexanes (5%-10%) to give 2-iodo-6-fluorobenzaldehyde oxime (7.06 g, 59% over 2 steps) as an oil that solidified over time. at 25-30° C. was added The reaction was stirred for 2 h was added at 25-30° C. extracted with Et2O The combined organic solution was washed with brine dried (MgSO4) filtered concentrated The residue was chromatographed on silica gel

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

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

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

Procedure: 2-Fluoro-6-iodo-benzaldehyde (3.0 g, 12 mmol), 1,3-propanediol (1.3 ml, 18 mmol), and para-toluenesulfonic acid (342 mg, 1.8 mmol) is heated at reflux in toluene (60 ml) using a Dean-Stark apparatus for 2 hours. The organic layer is washed with brine and dried over MgSO4 and evaporated to afford the desired compound (3.65 g). for 2 hours The organic layer is washed with brine dried over MgSO4 evaporated

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

Procedure: Buthyllithium (1.6 M, 60 ml, 0.113 mol) is added to an ice cooled solution of diisopropyl-amine (17.6 ml, 0.124 mol) in THF (200 ml). The solution is stirred at 0° C. for 30 minutes and is cooled to −78° C. 1-Fluoro-3-iodo-benzene (25 g, 0.113 mol) in THF (20 ml) is slowly added to the preformed LDA mixture. The resulting solution is stirred for another hour after which DMF (9.55 ml, 0.124 mol) is added and stirring is continued for another 30 minutes at −78° C. The reaction is quenched first with acetic acid (20 ml) followed by water (200 ml). The mixture is extracted with ether. The organic layer is washed with a 2N HCl solution, brine, is dried over MgSO4 and evaporated to afford the desired compound (28.3 g). is cooled to −78° C is added stirring is continued for another 30 minutes at −78° C The reaction is quenched first with acetic acid (20 ml) The mixture is extracted with ether The organic layer is washed with a 2N HCl solution, brine is dried over MgSO4 evaporated