2-chloro-5-methoxy-1,3-dimethylbenzene

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

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

Procedure: To a 1 L round-bottom flask 4-chloro-3,5-dimethylphenol 63 (20 g, 127.7 mmol) and acetone (500 mL, 0.2 M) was placed. To this solution were added potassium carbonate (35.3 g, 255.4 mmol) and iodomethane (63.44 g, 447 mmol). The reaction was stirred and heated to reflux for 3 hours. The reaction mixture was poured into water and extracted with ethyl acetate. The separated organic layer was washed with brine, dried over magnesium sulfate and concentrated. The crude product was purified by silica gel chromatography eluted with hexane to yield 4-chloro-3,5-dimethylphenyl methyl ether 64 (16.88 g, 77%). 1HNMR (300 MHz, CDCl3): δ 2.41 (s, 3H), 2.59 (s, 3H), 2.62 (s, 3H), 2.68 (s, 3H), 3.82 (s, 3H), 4.06 (s, 3H), 4.11 (s, 2H), 5.97 (d, 1H), 6.44 (s, 1H), 6.70 (s, 1H), 7.15 (d, 1H), 8.41 (brd, 1H), 10.31 (brd, 1H), APCI-MS m/z 468.2 (M+H)+. heated to reflux for 3 hours extracted with ethyl acetate The separated organic layer was washed with brine dried over magnesium sulfate concentrated The crude product was purified by silica gel chromatography eluted with hexane

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

Procedure: To a 1 L round-bottom flask 4-chloro-3,5-dimethylphenol 63 (20 g, 127.7 mmol) and acetone (500 mL, 0.2 M) was placed. To this solution were added potassium carbonate (35.3 g, 255.4 mmol) and iodomethane (63.44 g, 447 mmol). The reaction was stirred and heated to reflux for 3 hours. The reaction mixture was poured into water and extracted with ethyl acetate. The separated organic layer was washed with brine, dried over magnesium sulfate and concentrated. The crude product was purified by silica gel chromatography eluted with hexane to yield 4-chloro-3,5-dimethylphenyl methyl ether 64 (16.88 g, 77%). 1HNMR (300 MHz, CDCl3): δ 2.41 (s, 3H), 2.59 (s, 3H), 2.62 (s, 3H), 2.68 (s, 3H), 3.82 (s, 3H), 4.06 (s, 3H), 4.11 (s, 2H), 5.97 (d, 1H), 6.44 (s, 1H), 6.70 (s, 1H), 7.15 (d, 1H), 8.41 (brd, 1H), 10.31 (brd, 1H), APCI-MS m/z 468.2 (M+H)+. heated to reflux for 3 hours extracted with ethyl acetate The separated organic layer was washed with brine dried over magnesium sulfate concentrated The crude product was purified by silica gel chromatography eluted with hexane

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

Procedure: To a 1 L round-bottom flask 4-chloro-3,5-dimethylphenol 63 (20 g, 127.7 mmol) and acetone (500 mL, 0.2 M) was placed. To this solution were added potassium carbonate (35.3 g, 255.4 mmol) and iodomethane (63.44 g, 447 mmol). The reaction was stirred and heated to reflux for 3 hours. The reaction mixture was poured into water and extracted with ethyl acetate. The separated organic layer was washed with brine, dried over magnesium sulfate and concentrated. The crude product was purified by silica gel chromatography eluted with hexane to yield 4-chloro-3,5-dimethylphenyl methyl ether 64 (16.88 g, 77%). 1HNMR (300 MHz, CDCl3): δ 2.41 (s, 3H), 2.59 (s, 3H), 2.62 (s, 3H), 2.68 (s, 3H), 3.82 (s, 3H), 4.06 (s, 3H), 4.11 (s, 2H), 5.97 (d, 1H), 6.44 (s, 1H), 6.70 (s, 1H), 7.15 (d, 1H), 8.41 (brd, 1H), 10.31 (brd, 1H), APCI-MS m/z 468.2 (M+H)+. heated to reflux for 3 hours extracted with ethyl acetate The separated organic layer was washed with brine dried over magnesium sulfate concentrated The crude product was purified by silica gel chromatography eluted with hexane