1-(4-hydroxy-3,5-dimethylphenyl)ethanone

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: To an ice-cooled solution of 2,6-dimethylphenol (12.2 g, 0.1 mmol) in dichloromethane, anhydrous aluminum chloride (14.4 g) was slowly added with stirring, followed by slow addition of acetyl chloride (9.4 g). The reaction mixture was stirred at 10° C. or below for 1 h, then at room temperature for 3 h. Thereafter, the mixture was poured into ice water. Then, the reaction product was extracted with dichloromethane and the extracted layer was washed with water. Further, the extracted layer was dried over anhydrous sodium sulfate and the solvent was distilled off under reduced pressure. The residue was recrystallized with benzene, giving the desired compound, 2,6-dimethyl-4-acetylphenol in an amount of 1.9 g. was slowly added The reaction mixture was stirred at 10° C. or below for 1 h Then, the reaction product was extracted with dichloromethane the extracted layer was washed with water Further, the extracted layer was dried over anhydrous sodium sulfate the solvent was distilled off under reduced pressure The residue was recrystallized with benzene

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (36.6 g, 0.30 mol) of 2,6-dimethylphenol are mixed in an Hastelloy C autoclave with 0.315 mol of acetic anhydride and 9 mols of hydrogen fluoride. The temperature is raised to 50° C. and the reaction runs for 3 hours. After extraction and wash, 47.4 g of a gray to purple solid mass of 3,5-dimethyl-4-hydroxyacetophenone is obtained. This solid is then esterified by refluxing with 4 mols of acetic anhydride for 19 hours. After removal of acetic acid and acetic anhydride by vacuum distillation the 3,5-dimethyl-4-acetoxyacetophenone is flash distilled to yield 47.7 g of a slightly yellow liquid. 0.1 mol of the 3,5-dimethyl-4-acetoxyacetophenone, 1.2 g of 5% Pd/C as catalyst and 100 ml ethanol are mixed in an autoclave and the autoclave is charged with hydrogen gas at a pressure of 215-220 mm Hg PSIG and the reaction is run for about 21/2 hours at a temperature of about 25°-30° C. Additional catalyst is added as needed. The catalyst is then removed and the ethanol evaporated to yield 21.5 g of a colorless oil which is 1-(3',5'-dimethyl-4'-acetoxyphenyl)ethanol. 0.168 mol of 1-(3',5'-dimethyl-4'-acetoxyphenyl)ethanol is added to a flask with 0.35 g KHSO4 and 0.5 g t-butyl catechol. The flask is heated to 185° to 190° C. at 1.5 to 2.0 mm Hg. A colorless liquid is distilled. After the addition of 0.15 g of t-butyl catechol, and redistillation, 26.1 g of 3,5- dimethyl-4-acetoxystyrene monomer is produced. The compound has a boiling point of 90°-91° C. at 0.5 mm of Hg and the yield is 81.8%. After extraction wash

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

Procedure: To an ice-cooled solution of 2,6-dimethylphenol (12.2 g, 0.1 mmol) in dichloromethane, anhydrous aluminum chloride (14.4 g) was slowly added with stirring, followed by slow addition of acetyl chloride (9.4 g). The reaction mixture was stirred at 10° C. or below for 1 h, then at room temperature for 3 h. Thereafter, the mixture was poured into ice water. Then, the reaction product was extracted with dichloromethane and the extracted layer was washed with water. Further, the extracted layer was dried over anhydrous sodium sulfate and the solvent was distilled off under reduced pressure. The residue was recrystallized with benzene, giving the desired compound, 2,6-dimethyl-4-acetylphenol in an amount of 1.9 g. was slowly added The reaction mixture was stirred at 10° C. or below for 1 h Then, the reaction product was extracted with dichloromethane the extracted layer was washed with water Further, the extracted layer was dried over anhydrous sodium sulfate the solvent was distilled off under reduced pressure The residue was recrystallized with benzene

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: 1-(5′-Fluoro-2′-methoxy-2,6-dimethyl-biphenyl-4-yl)-ethylamine was prepared in a similar manner to 1-(2-allyl-5′-fluoro-2′-methoxy-biphenyl-4-yl)-ethylamine (Example 34) using 3,5-dimethyl-4-hydroxy acetophenone instead of 3′-allyl-4′-hydroxyacetophenone. The title compound was prepared in a similar manner to N-[1-(2-allyl-5′-fluoro-2′-methoxy-biphenyl-4-yl)-ethyl]-3,4-difluoro-benzenesulfonamide (Example 34) using 1-(5′-fluoro-2′-methoxy-2,6-dimethyl-biphenyl-4-yl)-ethylamine and 3,5-dimethyl-isoxazole-4-sulfonyl chloride. MS (ESI) m/z: 433.3 [M+H]+.

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

Procedure: 1-(5′-Fluoro-2′-methoxy-2,6-dimethyl-biphenyl-4-yl)-ethylamine was prepared in a similar manner to 1-(2-allyl-5′-fluoro-2′-methoxy-biphenyl-4-yl)-ethylamine (Example 34) using 3,5-dimethyl-4-hydroxy acetophenone instead of 3′-allyl-4′-hydroxyacetophenone. The title compound was prepared in a similar manner to N-[1-(2-allyl-5′-fluoro-2′-methoxy-biphenyl-4-yl)-ethyl]-3,4-difluoro-benzenesulfonamide (Example 34) using 1-(5′-fluoro-2′-methoxy-2,6-dimethyl-biphenyl-4-yl)-ethylamine and 3,5-dimethyl-isoxazole-4-sulfonyl chloride. MS (ESI) m/z: 433.3 [M+H]+.

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

Procedure: 1-(5′-Fluoro-2′-methoxy-2,6-dimethyl-biphenyl-4-yl)-ethylamine was prepared in a similar manner to 1-(2-allyl-5′-fluoro-2′-methoxy-biphenyl-4-yl)-ethylamine (Example 34) using 3,5-dimethyl-4-hydroxy acetophenone instead of 3′-allyl-4′-hydroxyacetophenone. The title compound was prepared in a similar manner to N-[1-(2-allyl-5′-fluoro-2′-methoxy-biphenyl-4-yl)-ethyl]-3,4-difluoro-benzenesulfonamide (Example 34) using 1-(5′-fluoro-2′-methoxy-2,6-dimethyl-biphenyl-4-yl)-ethylamine and 3,5-dimethyl-isoxazole-4-sulfonyl chloride. MS (ESI) m/z: 433.3 [M+H]+.

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: (36.6 g, 0.30 mol) of 2,6-dimethylphenol are mixed in an Hastelloy C autoclave with 0.315 mol of acetic anhydride and 9 mols of hydrogen flouride. The temperature is raised to 50° C. and the reaction runs for 3 hours. After extraction and wash, 47.4 g of a gray to purple solid mass of 3,5-dimethyl-4-hydroxyacetophenone is obtained. This solid is then esterified by refluxing with 4 mols of acetic anhydride for 19 hours. After removal of acetic acid and acetic anhydride by vacuum distillation the 3,5-dimethyl-4-acetoxyacetophenone is flash distilled to yield 47.7 g of a slightly yellow liquid. 0.1 mol of the 3,5-dimethyl-4-acetoxyacetophenone, 1.2 g of 5% Pd/C as catalyst and 100 ml ethanol are mixed in an autoclave and the autoclave is charged with hydrogen gas at a pressure of 215-220 mm Hg and the reaction is run for about 2 1/2 hours at a temperature of about 25°-30° C. Additional catalyst is added as needed. The catalyst is then removed and the ethanol evaporated to yield 21.5 g of a colorless oil which is (3,5-dimethyl-4-acetoxyphenyl)ethanol. 0.168 mol of (3,5-dimethyl-4-acetoxyphenyl)ethanol is added to a flask with 0.35 g KHSO4 and 0.5 g t-butyl catechol. The flask is heated to 185° to 190° C. at 1.5 to 2.0 mm Hg. A colorless liquid is distilled. After the addition of 0.15 g of t-butyl catechol, and redistillation, 26.1 g of 3,5- dimethyl-4-acetoxystyrene monomer is produced. The compound has a boiling point of 90-91°-91° C. at 0.5 mm of Hg and the yield is 81.8%. After extraction wash