3-bromo-4-methylbenzaldehyde

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: 11.8 g (60 mmol) of 3-bromo-4-methylbenzaldehyde are placed in 150 ml of toluene in a round-bottomed flask and under nitrogen. 16.5 ml (300 mmol) of ethylene glycol and 571 mg (3 mmol) of para-toluenesulfonic acid are added. The mixture is refluxed for 36 hours and the water formed is separated out using Dean-Stark apparatus. At room temperature, the reaction medium is poured into saturated aqueous sodium hydrogen carbonate solution and then extracted with ether. The organic phase is dried over magnesium sulfate, filtered and evaporated. 13 g (89%) of the expected product are obtained in the form of a brown oil. The mixture is refluxed for 36 hours is separated out At room temperature, the reaction medium is poured into saturated aqueous sodium hydrogen carbonate solution extracted with ether The organic phase is dried over magnesium sulfate filtered evaporated

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

Procedure: 11.8 g (60 mmol) of 3-bromo-4-methylbenzaldehyde are placed in 150 ml of toluene in a round-bottomed flask and under nitrogen. 16.5 ml (300 mmol) of ethylene glycol and 571 mg (3 mmol) of para-toluenesulfonic acid are added. The mixture is refluxed for 36 hours and the water formed is separated out using Dean-Stark apparatus. At room temperature, the reaction medium is poured into saturated aqueous sodium hydrogen carbonate solution and then extracted with ether. The organic phase is dried over magnesium sulfate, filtered and evaporated. 13 g (89%) of the expected product are obtained in the form of a brown oil. The mixture is refluxed for 36 hours is separated out At room temperature, the reaction medium is poured into saturated aqueous sodium hydrogen carbonate solution extracted with ether The organic phase is dried over magnesium sulfate filtered evaporated

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

Procedure: 14.4 g (72 mmol) of (3-bromo-4-methylphenyl)methanol are placed in 200 ml of dichloromethane in a round-bottomed flask. 62.6 g (72 mmol) of manganese oxide are added and the medium is stirred at room temperature overnight. The mixture is filtered through Celite and the solvent is evaporated off. 11.8 g (85%) of the expected product are obtained in the form of an oil. The mixture is filtered through Celite the solvent is evaporated off

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

Procedure: The product from Example 11B (0.34 g, 3.0 mmol), 3-bromo-4-methylbenzaldehyde (Pearson.; Org. Synth. Coll. Vol. V, 1973, 117) (0.60 g, 3.0 mmol) and methyl 3-aminocrotonate (0.35 g, 3.0 mmol) in methanol (8 mL) were heated at 80° C. in a sealed tube for 60 hours. After cooling to ambient temperature, the mixture was filtered and the filter cake washed with methanol and dried to provide the title compound (0.63 g). the mixture was filtered the filter cake washed with methanol dried

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

Procedure: This compound was prepared by using procedures analogous to those described for the synthesis of Example 75, Step 1 starting from 3-bromo-4-methylbenzaldehyde (Aldrich, Cat. #4017458) and. aminoacetaldehyde dimethyl acetal. Analytic LCMS (M+H)+: m/z=221.95/223.95. This compound was prepared

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

Procedure: To a stirred solution of 3-bromo-4-methylbenzyl alcohol (4.43 g, 22 mMol) in CHCl3 (100 mL) was added MnO2 (15 g, 172 mMol). The reaction was stirred and refluxed (70° C. oil bath) for 18 h, cooled to RT, filtered through Celite®, rinsed with CHCl3, and concentrated to dryness under vacuum. Purification by flash chromatography on silica gel (10% EtOAc, hexanes) gave the title product (3.0 g, 68%). 1H NMR (400 MHz, CDCl3) δ 9.98 (s, 1H), 7.75 (d, J=1.5 Hz, 1 H), 7.73 (d, J=8.1 Hz, 1 H), 7.57 (dd, J=8.1, 1.5 Hz, 1 H), 7.28 (s, 1 H), 2.50 (s, 3 H). cooled to RT filtered through Celite® rinsed with CHCl3 concentrated to dryness under vacuum Purification by flash chromatography on silica gel (10% EtOAc, hexanes)

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

Procedure: To a stirred solution of 3-bromo-4-methylbenzyl alcohol (4.43 g, 22 mMol) in CHCl3 (100 mL) was added MnO2 (15 g, 172 mMol). The reaction was stirred and refluxed (70° C. oil bath) for 18 h, cooled to RT, filtered through Celite®, rinsed with CHCl3, and concentrated to dryness under vacuum. Purification by flash chromatography on silica gel (10% EtOAc, hexanes) gave the title product (3.0 g, 68%). 1H NMR (400 MHz, CDCl3) δ 9.98 (s, 1H), 7.75 (d, J=1.5 Hz, 1 H), 7.73 (d, J=8.1 Hz, 1 H), 7.57 (dd, J=8.1, 1.5 Hz, 1 H), 7.28 (s, 1 H), 2.50 (s, 3 H). cooled to RT filtered through Celite® rinsed with CHCl3 concentrated to dryness under vacuum Purification by flash chromatography on silica gel (10% EtOAc, hexanes)

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

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

Procedure: (3-bromo-4-methylphenyl)methanol was oxidized as follows: To the primary alcohol (15 mmol) in methylene chloride (30 mL) was added 10 equivalents of activated manganese oxide (IV). The mixture was stirred at room temperature for 24 hours, the filtered through a bed of celite. Removal of the solvent left a yellow solid. Product was used crude in next step without further purification. The yield was 89%. 1H NMR (Varian 300 MHz CDCl3, shifts relative to the solvent peak at 7.24 ppm) δ 9.8 (s, 1H) 8.0 (s, 1H) 7.7 (d, 1H), 7.2 (d, 1H), 2.3 (s, 3H). the filtered through a bed of celite Removal of the solvent left a yellow solid without further purification