4-methoxy-2,6-dimethylbenzaldehyde

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

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 8-amino-2,3-dimethylimidazo[1,2-a]pyridine (0.5 g, 3.1 mmol), 4-methoxy-2.6-dimethylbenzaldehyd (0.51 g, 3.11 mmol) were dissolved in methanol (10 ml) whereupon zinc chloride (0.51 g, 3.82 mmol) dissolved in methanol (5 ml) was added. Sodium cyanoborohydride was added in portions and the mixture was refluxed for 3 h under under nitrogen. The mixture was stirred at 0-5° C. and 1 M sodium hydroxide (20 ml) was added. After extraction with 2×50 ml of methylene chloride the combined organic layer was washed with water and dried over sodium sulfate. The solvent was removed under reduced pressure. The residue was chromatographed on silica (dichloromethane: ethyl acetate, 1:1) yielding 0.58 g 60% of the title compound. was added the mixture was refluxed for 3 h under under nitrogen After extraction with 2×50 ml of methylene chloride the combined organic layer was washed with water dried over sodium sulfate The solvent was removed under reduced pressure The residue was chromatographed on silica (dichloromethane: ethyl acetate, 1:1)

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

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

Procedure: To 4-bromo-2-isopropylanisole (a compound of Formula 3 from Example 2) (12 g, 52.4 mmol) in 300 mL of THF at -78° C. was added 68 mL of tert-butyllithium (1.7 M in pentane). The reaction mixture was stirred for 10 min at -78° C. and then 2,6-dimethyl-4-methoxybenzaldehyde (a compound of Formula 6 from Example 4) (8.6 g, 52.4 mmol) was added. The reaction mixture was stirred for 1 hour at -78° C. and for 1.5 hours at room temperature, diluted with 150 mL of ether, washed with 150 mL of water, acidified with 1N HCl, and washed with 5×50 mL of brine. The organic portion was dried (MgSO4), filtered, and evaporated to give the crude product, which was purified by flash column chromatography (silica gel, 95:5 hexane/ethylacetate) to yield 3,5-dimethyl-4-(3'-isopropyl-4'-methoxybenzylhydroxy) anisole (7) (12 g, 38.2 mmol, 73%) as an oil; 1HNMR (CDCl3) δ1.2 (dd, 6H), 2.27 (s, 6H), 3.30 (heptet, 1H), 3.80 (s, 6H), 6.26 (s, 1H), 6.59 (s, 2H), 6.76 (d, 1H), 6.89 (d, 1H), 7.24 (s, 1H). The reaction mixture was stirred for 1 hour at -78° C. and for 1.5 hours at room temperature washed with 150 mL of water washed with 5×50 mL of brine The organic portion was dried (MgSO4) filtered evaporated to give the crude product, which was purified by flash column chromatography (silica gel, 95:5 hexane/ethylacetate)

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

Procedure: To 4-bromo-3,5-dimethylanisole (a compound of Formula 5 from Example 3) (20 g, 93.0 mmol) in 500 mL of THF at -78° C. was added 120 mL of tert-Butyllithium (1.7 M in pentane). The reaction mixture was stirred for 30 minutes at -78° C. and then DMF (136.0 g, 186.0 mmol) was added. The reaction mixture was stirred for 1 hour at -78° C. and for 1.5 hours at room temperature, diluted with 300 mL of ether, washed with 300 mL of water, acidified 1N HC1, and 5×100 mL of brine. The organic portion was dried (MgSO4), filtered, and evaporated to give the crude product, which was purified by flash column chromatography (silica gel, 90:10 hexane/ethylacetate) to yield 2,6-dimethyl-4-methoxybenzaldehyde (a compound of Formula 6), (9.50 g, 57.8 mmol, 62%) as a white solid; 1HNMR (CDCl3 δ2.61 (s, 6H), 3.83 (s, 3H), 6.6 (s, 2H), 10.5 (s, 1H). The reaction mixture was stirred for 1 hour at -78° C. and for 1.5 hours at room temperature washed with 300 mL of water The organic portion was dried (MgSO4) filtered evaporated to give the crude product, which was purified by flash column chromatography (silica gel, 90:10 hexane/ethylacetate)

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

Procedure: To 4-bromo-2-isopropylanisole (3) (12 g, 52.4 mmol) in 300 mL of tetrahydrofuran at -78° C. was added 68 mL of tert-Butyllithium (1.7M in pentane). The reaction mixture was stirred for 10 min at -78° C. and then 2,6-dimethyl-4-methoxybenzaldehyde (6) (8.6 g, 52.4 mmol) was added. The reaction mixture was stirred for 1 hour at -78° C. and for 1.5 hours at room temperature, diluted with 150 mL of ether, washed with 150 mL of water, acidified with 1N HCl, and washed with 5×50 mL of brine. The organic portion was dried (MgSO4), filtered, and evaporated to give the crude product, which was purified by flash column chromatography (silica gel, 95:5 hexane/ethylacetate) to yield 3,5-dimethyl-4-(3'-isopropyl-4'-methoxybenzylhydroxy) anisole (7) (12 g, 38.2 mmol, 73%) as an oil; 1HNMR (CDC13) δ 1.2 (dd, 6H), 2.27 (s, 6H), 3.30 (heptet, 1H), 3.80 (s, 6H), 6.26 (s, 1H), 6.59 (s, 2H) 6.76 (d, 1H), 6.89 (d, 1H), 7.24 (s, 1H). The reaction mixture was stirred for 1 hour at -78° C. and for 1.5 hours at room temperature washed with 150 mL of water washed with 5×50 mL of brine The organic portion was dried (MgSO4) filtered evaporated to give the crude product, which was purified by flash column chromatography (silica gel, 95:5 hexane/ethylacetate)

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

Procedure: To 4-bromo-3,5-dimethylanisole (20 g, 93.0 mmol) in 500 mL of tetrahydrofuran at -78° C. was added 120 mL of tert-Butyllithium (1.7M in pentane). The reaction mixture was stirred for 30 minutes at -78° C. and then DMF (136.0 g, 186.0 mmol) was added. The reaction mixture was stirred for 1 hour at -78° C. and for 1.5 hours at room temperature, diluted with 300 mL of ether, washed with 300 mL of water, acidified 1N HCl , and 5×100 mL of brine. The organic portion was dried (MgSO4), filtered, and evaporated to give the crude product, which was purified by flash column chromatography (silica gel, 90:10 hexane/ethylacetate) to yield 2,6-dimethyl-4-methoxybenzaldehyde (6), (9.50 g, 57.8 mmol, 62%) as a white solid; 1HNMR (CDCl3 δ 2.61 (s, 6H), 3.83 (s, 3H), 6.6 (s, 2H), 10.5 (s, 1H). The reaction mixture was stirred for 1 hour at -78° C. and for 1.5 hours at room temperature washed with 300 mL of water The organic portion was dried (MgSO4) filtered evaporated to give the crude product, which was purified by flash column chromatography (silica gel, 90:10 hexane/ethylacetate)

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 8-amino-2,3-dimethylimidazo[1,2-a]pyridine (0.5 g, 3.1 mmol), 4-methoxy-2.6-dimethylbenzaldehyd (0.51 g, 3.11 mmol) were dissolved in methanol (10 ml) whereupon zinc chloride (0.51 g, 3.82 mmol) dissolved in methanol (5 ml) was added. Sodium cyanoborohydride was added in portions and the mixture was refluxed for 3 h under under nitrogen. The mixture was stirred at 0-5° C. and 1 M sodium hydroxide (20 ml) was added. After extraction with 2×50 ml of methylene chloride the combined organic layer was washed with water and dried over sodium sulfate. The solvent was removed under reduced pressure. The residue was chromatographed on silica (dichloromethane: ethyl acetate. 1:1) yielding 0.58 g 60% of the title compound. was added the mixture was refluxed for 3 h under under nitrogen After extraction with 2×50 ml of methylene chloride the combined organic layer was washed with water dried over sodium sulfate The solvent was removed under reduced pressure The residue was chromatographed on silica (dichloromethane: ethyl acetate. 1:1)

Conditions: temp:2.51; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 8-amino-2,3-dimethylimidazo[1,2-a]pyridine (0.5 g, 3.1 mmol), 4-methoxy-2.6-dimethylbenzaldehyd (0.51 g, 3.11 mmol) were dissolved in methanol (10 ml) whereupon zinc chloride (0.51 g, 3.82 mmol) dissolved in methanol (5 ml) was added. Sodium cyanoborohydride was added in portions and the mixture was refluxed for 3 h under under nitrogen. The mixture was stirred at 0-5° C. and 1 M sodium hydroxide (20 ml) was added. After extraction with 2×50 ml of methylene chloride the combined organic layer was washed with water and dried over sodium sulfate. The solvent was removed under reduced pressure. The residue was chromatographed on silica (dichloromethane: ethyl acetate, 1:1) yielding 0.58 g 60% of the title compound. was added the mixture was refluxed for 3 h under under nitrogen After extraction with 2×50 ml of methylene chloride the combined organic layer was washed with water dried over sodium sulfate The solvent was removed under reduced pressure The residue was chromatographed on silica (dichloromethane: ethyl acetate, 1:1)