6-bromo-2,2-dimethyl-3H-thiochromen-4-one

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

Procedure: To a cold (-78° C.) solution of 2-methylthiophene (1.2 g, 12.2 mmol) in THF (8 mL) was added n-BuLi in hexane (1.6M, 8.5 mL). The mixture was warmed to ambient temperature over 30 minutes. with stirring. The mixture was recooled to -78° C. and a solution of 2,2-dimethyl-6-bromo-thiochroman-4-one (Compound M, 1.4 g, 5.2 mmol) in THF (10 mL) was added. The mixture was stirred for 16 hours at ambient temperature. Then the reaction mixture was diluted with ether (125 mL), washed with water (10 mL), brine (10 mL) dried and the solvent was removed by evaporation. The product was seperated by column chromatography and was dissolved in dichloromethane (5 mL). To this solution p-TSA (5 mg) was added and the mixture was stirred at ambient temperature for 5 min. The reaction was quenched with 10% NaHCO3 (3 mL), washed with brine (5 mL), dried and the solvent was removed by distillation. The residual crude material was purified by column chromatography to obtain the title compound as a pale yellow oil. was recooled to -78° C. The mixture was stirred for 16 hours at ambient temperature washed with water (10 mL), brine (10 mL) dried the solvent was removed by evaporation The product was seperated by column chromatography was dissolved in dichloromethane (5 mL) To this solution p-TSA (5 mg) was added the mixture was stirred at ambient temperature for 5 min The reaction was quenched with 10% NaHCO3 (3 mL) washed with brine (5 mL) dried the solvent was removed by distillation The residual crude material was purified by column chromatography

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

Procedure: To a cold (-78° C.) solution of 4-bromotoluene (720 mg, 4.2 mmol) in THF (8 mL) was added t-BuLi in pentane (1.7M, 0.5 mL, 0.85 mmol). The mixture was warmed to ambient temperature over 30 minutes with stirring. This mixture was added to a flask containing 2,2-dimethyl-6-bromo-thiochroman-4-one (Compound M, 140 mg, 0.4 mmol) and THF (2 mL). and stirred for 16 hours at ambient temperature. The reaction was quenched by adding aq. NH4Cl, and the resulting mixture was extracted with ethylacetate, washed with brine, dried and the solvent was removed by evaporation. The product was isolated by chromatography on silica gel. The material was dissolved in dichloromethane (5 mL) and pTSA (5 mg) was added and heated to 50° C. for 3 hours. The misture was diluted with ethylacetate (20 mL), washed with 10% NaHCO3 (5 mL), brine (5 mL), dried with MgSO4 and the solvent was removed by evaporation to afford the title compound as an off. This mixture was added to a flask and stirred for 16 hours at ambient temperature The reaction was quenched by adding aq. NH4Cl the resulting mixture was extracted with ethylacetate washed with brine dried the solvent was removed by evaporation The product was isolated by chromatography on silica gel heated to 50° C. for 3 hours washed with 10% NaHCO3 (5 mL), brine (5 mL) dried with MgSO4 the solvent was removed by evaporation

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

Procedure: To a cold (-78° C.) solution of 2-methylthiophene (1.2 g, 12.2 mmol) in THF (8 mL) was added n-BuLi in hexane (1.6M, 8.5 mL). The mixture was warmed to ambient temperature over 30 minutes. with stirring. The mixture was recooled to -78° C. and a solution of 2,2-dimethyl-6-bromo-thiochroman-4-one (Compound M, 1.4 g, 5.2 mmol) in THF (10 mL) was added. The mixture was stirred for 16 hours at ambient temperature. Then the reaction mixture was diluted with ether (125 mL), washed with water (10 mL), brine (10 mL) dried and the solvent was removed by evaporation. The product was seperated by column chromatography and was dissolved in dichloromethane (5 mL). To this solution p-TSA (5 mg) was added and the mixture was stirred at ambient temperature for 5 min. The reaction was quenched with 10% NaHCO3 (3 mL), washed with brine (5 mL), dried and the solvent was removed by distillation. The residual crude material was purified by column chromatography to obtain the title compound as a pale yellow oil. was recooled to -78° C. The mixture was stirred for 16 hours at ambient temperature washed with water (10 mL), brine (10 mL) dried the solvent was removed by evaporation The product was seperated by column chromatography was dissolved in dichloromethane (5 mL) To this solution p-TSA (5 mg) was added the mixture was stirred at ambient temperature for 5 min The reaction was quenched with 10% NaHCO3 (3 mL) washed with brine (5 mL) dried the solvent was removed by distillation The residual crude material was purified by column chromatography

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

Procedure: To a cold (-78° C.) solution of 4-bromotoluene (720 mg, 4.2 mmol) in THF (8 mL) was added t-BuLi in pentane (1.7M, 0.5 mL, 0.85 mmol). The mixture was warmed to ambient temperature over 30 minutes with stirring. This mixture was added to a flask containing 2,2-dimethyl-6-bromo-thiochroman-4-one (Compound M, 140 mg, 0.4 mmol) and THF (2 mL). and stirred for 16 hours at ambient temperature. The reaction was quenched by adding aq. NH4Cl, and the resulting mixture was extracted with ethylacetate, washed with brine, dried and the solvent was removed by evaporation. The product was isolated by chromatography on silica gel. The material was dissolved in dichloromethane (5 mL) and pTSA (5 mg) was added and heated to 50° C. for 3 hours. The misture was diluted with ethylacetate (20 mL), washed with 10% NaHCO3 (5 mL), brine (5 mL), dried with MgSO4 and the solvent was removed by evaporation to afford the title compound as an off. This mixture was added to a flask and stirred for 16 hours at ambient temperature The reaction was quenched by adding aq. NH4Cl the resulting mixture was extracted with ethylacetate washed with brine dried the solvent was removed by evaporation The product was isolated by chromatography on silica gel heated to 50° C. for 3 hours washed with 10% NaHCO3 (5 mL), brine (5 mL) dried with MgSO4 the solvent was removed by evaporation

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

Procedure: To a cold (-78° C.) solution of 2-methylthiophene (1.2 g, 12.2 mmol) in THF (8 mL) was added n-BuLi in hexane (1.6M, 8.5 mL). The mixture was warmed to ambient temperature over 30 minutes with stirring. The mixture was recooled to -78° C. and a solution of 2,2-dimethyl-6-bromo-thiochroman-4-one (Compound M, 1.4 g, 5.2 mmol) in THF (10 mL) was added. The mixture was stirred for 16 hours at ambient temperature. Then the reaction mixture was diluted with ether (125 mL), washed with water (10 mL), brine (10 mL) dried and the solvent was removed by evaporation. The product was seperated by column chromatography and was dissolved in dichloromethane (5 mL). To this solution p-TSA (5 mg) was added and the mixture was stirred at ambient temperature for 5 min. The reaction was quenched with 10% NaHCO3 (3 mL), washed with brine (5 mL), dried and the solvent was removed by distillation. The residual crude material was purified by column chromatography to obtain the title compound as a pale yellow oil. was recooled to -78° C. The mixture was stirred for 16 hours at ambient temperature washed with water (10 mL), brine (10 mL) dried the solvent was removed by evaporation The product was seperated by column chromatography was dissolved in dichloromethane (5 mL) To this solution p-TSA (5 mg) was added the mixture was stirred at ambient temperature for 5 min The reaction was quenched with 10% NaHCO3 (3 mL) washed with brine (5 mL) dried the solvent was removed by distillation The residual crude material was purified by column chromatography

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

Procedure: To a cold (-78° C.) solution of 4-bromotoluene (720 mg, 4.2 mmol) in THF (8 mL) was added t-BuLi in pentane (1.7M, 0.5 mL, 0.85 mmol). The mixture was warmed to ambient temperature over 30 minutes with stirring. This mixture was added to a flask containing 2,2-dimethyl-6-bromo-thiochroman-4-one (Compound M, 140 mg, 0.4 mmol) and THF (2 mL). and stirred for 16 hours at ambient temperature. The reaction was quenched by adding aq. NH4Cl, and the resulting mixture was extracted with ethylacetate, washed with brine, dried and the solvent was removed by evaporation. The product was isolated by chromatography on silica gel. The material was dissolved in dichloromethane (5 mL) and pTSA (5 mg) was added and heated to 50° C. for 3 hours. The misture was diluted with ethylacetate (20 mL), washed with 10% NaHCO3 (5 mL), brine (5 mL), dried with MgSO4 and the solvent was removed by evaporation to afford the title compound as an oil. This mixture was added to a flask and stirred for 16 hours at ambient temperature The reaction was quenched by adding aq. NH4Cl the resulting mixture was extracted with ethylacetate washed with brine dried the solvent was removed by evaporation The product was isolated by chromatography on silica gel heated to 50° C. for 3 hours washed with 10% NaHCO3 (5 mL), brine (5 mL) dried with MgSO4 the solvent was removed by evaporation

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

Procedure: To a cold (-78° C.) solution of 4-bromotoluene (720 mg, 4.2 mmol) in THF (8 mL) was added t-BuLi in pentane (1.7M, 0.5 mL, 0.85 mmol). The mixture was warmed to ambient temperature over 30 minutes with stirring. This mixture was added to a flask containing 2,2-dimethyl-6-bromo-thiochroman-4-one (Compound M, 140 mg, 0.4 mmol) and THF (2 mL). and stirred for 16 hours at ambient temperature. The reaction was quenched by adding aq. NH4Cl, and the resulting mixture was extracted with ethylacetate, washed with brine, dried and the solvent was removed by evaporation. The product was isolated by chromatography on silica gel. The material was dissolved in dichloromethane (5 mL) and pTSA (5 mg) was added and heated to 50° C. for 3 hours. The misture was diluted with ethylacetate (20 mL), washed with 10% NaHCO3 (5 mL), brine (5 mL), dried with MgSO4 and the solvent was removed by evaporation to afford the title compound as an oil. This mixture was added to a flask and stirred for 16 hours at ambient temperature The reaction was quenched by adding aq. NH4Cl the resulting mixture was extracted with ethylacetate washed with brine dried the solvent was removed by evaporation The product was isolated by chromatography on silica gel heated to 50° C. for 3 hours washed with 10% NaHCO3 (5 mL), brine (5 mL) dried with MgSO4 the solvent was removed by evaporation

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

Procedure: To a cold (−78° C.) solution of 2-methylthiophene (1.2 g, 12.2 mmol) in THF (8 mL) was added n-BuLi in hexane (1.6M, 8.5 mL). The mixture was warmed to ambient temperature over 30 minutes. with stirring. The mixture was recooled to −78° C. and a solution of 2,2-dimethyl-6-bromo-thiochroman4-one (Compound M, 1.4 g, 5.2 mmol) in THF (10 mL) was added. The mixture was stirred for 16 hours at ambient temperature. Then the reaction mixture was diluted with ether (125 mL), washed with water (10 mL), brine (10 mL) dried and the solvent was removed by evaporation. The product was seperated by column chromatography and was dissolved in dichloromethane (5 mL). To this solution p-TSA (5 mg) was added and the mixture was stirred at ambient temperature for 5 min. The reaction was quenched with 10% NaHCO3 (3 mL), washed with brine (5 mL), dried and the solvent was removed by distillation. The residual crude a material was purified by column chromatography to obtain the title compound as a pale yellow oil. was recooled to −78° C. The mixture was stirred for 16 hours at ambient temperature washed with water (10 mL), brine (10 mL) dried the solvent was removed by evaporation The product was seperated by column chromatography was dissolved in dichloromethane (5 mL) To this solution p-TSA (5 mg) was added the mixture was stirred at ambient temperature for 5 min The reaction was quenched with 10% NaHCO3 (3 mL) washed with brine (5 mL) dried the solvent was removed by distillation The residual crude a material was purified by column chromatography

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

Procedure: To a cold (−78° C.) solution of 4-bromotoluene (720 mg, 4.2 mmol) in THF (8 mL) was added t-BuLi in pentane (1.7M, 0.5 mL, 0.85 mmol). The mixture was warmed to ambient temperature over 30 minutes with stirring. This mixture was added to a flask containing 2,2-dimethyl-6-bromo-thiochroman-4-one (Compound M, 140 mg, 0.4 mmol) and THF (2 mL). and stirred for 16 hours at ambient temperature. The reaction was quenched by adding aq. NH4Cl, and the resulting mixture was extracted with ethylacetate, washed with brine, dried and the solvent was removed by evaporation. The product was isolated by chromatography on silica gel. The material was dissolved in dichloromethane (5 mL) and pTSA (5 mg) was added and heated to 50° C. for 3 hours. The mixture was diluted with ethylacetate (20 mL), washed with 10% NaHCO3 (5 mL), brine (5 mL), dried with MgSO4 and the solvent was removed by evaporation to afford the title compound as an oil. This mixture was added to a flask and stirred for 16 hours at ambient temperature The reaction was quenched by adding aq. NH4Cl the resulting mixture was extracted with ethylacetate washed with brine dried the solvent was removed by evaporation The product was isolated by chromatography on silica gel heated to 50° C. for 3 hours washed with 10% NaHCO3 (5 mL), brine (5 mL) dried with MgSO4 the solvent was removed by evaporation

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

Procedure: To a cold (−78° C.) solution of 2-methylthiophene (1.2 g, 12.2 mmol) in THF (8 mL) was added n-BuLi in hexane (1.6M, 8.5 mL). The mixture was warmed to ambient temperature over 30 minutes. with stirring. The mixture was recooled to −78° C. and a solution of 2,2-dimethyl-6-bromo-thiochroman-4-one (Compound M, 1.4 g, 5.2 mmol) in THF (10 mL) was added. The mixture was stirred for 16 hours at ambient temperature. Then the reaction mixture was diluted with ether (125 mL), washed with water (10 mL), brine (10 mL) dried and the solvent was removed by evaporation. The product was seperated by column chromatography and was dissolved in dichloromethane (5 mL). To this solution p-TSA (5 mg) was added and the mixture was stirred at ambient temperature for 5 min. The reaction was quenched with 10% NaHCO3 (3 mL), washed with brine (5 mL), dried and the solvent was removed by distillation. The residual crude material was purified by column chromatography to obtain the title compound as a pale yellow oil. was recooled to −78° C. The mixture was stirred for 16 hours at ambient temperature washed with water (10 mL), brine (10 mL) dried the solvent was removed by evaporation The product was seperated by column chromatography was dissolved in dichloromethane (5 mL) To this solution p-TSA (5 mg) was added the mixture was stirred at ambient temperature for 5 min The reaction was quenched with 10% NaHCO3 (3 mL) washed with brine (5 mL) dried the solvent was removed by distillation The residual crude material was purified by column chromatography

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

Procedure: To a cold (-78° C.) solution of 2-methylthiophene (1.2 g, 12.2 mmol) in THF (8 mL) was added n-BuLi in hexane (1.6M, 8.5 mL). The mixture was warmed to ambient temperature over 30 minutes. with stirring. The mixture was recooled to -78° C. and a solution of 2,2-dimethyl-6-bromo-thiochroman-4-one (Compound M, 1.4 g, 5.2 mmol) in THF (10 mL) was added. The mixture was stirred for 16 hours at ambient temperature. Then the reaction mixture was diluted with ether (125 mL), washed with water (10 mL), brine (10 mL) dried and the solvent was removed by evaporation. The product was seperated by column chromatography and was dissolved in dichloromethane (5 mL). To this solution p-TSA (5 mg) was added and the mixture was stirred at ambient temperature for 5 min. The reaction was quenched with 10% NaHCO3 (3 mL), washed with brine (5 mL), dried and the solvent was removed by distillation. The residual crude material was purified by column chromatography to obtain the title compound as a pale yellow oil. was recooled to -78° C. The mixture was stirred for 16 hours at ambient temperature washed with water (10 mL), brine (10 mL) dried the solvent was removed by evaporation The product was seperated by column chromatography was dissolved in dichloromethane (5 mL) To this solution p-TSA (5 mg) was added the mixture was stirred at ambient temperature for 5 min The reaction was quenched with 10% NaHCO3 (3 mL) washed with brine (5 mL) dried the solvent was removed by distillation The residual crude material was purified by column chromatography

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

Procedure: To a cold (-78° C.) solution of 4-bromotoluene (720 mg, 4.2 mmol) in THF (8 mL) was added t-BuLi in pentane (1.7M, 0.5 mL, 0.85 mmol). The mixture was warmed to ambient temperature over 30 minutes with stirring. This mixture was added to a flask containing 2,2-dimethyl-6-bromo-thiochroman-4-one (Compound M, 140 mg, 0.4 mmol) and THF (2 mL). and stirred for 16 hours at ambient temperature. The reaction was quenched by adding aq. NH4Cl, and the resulting mixture was extracted with ethylacetate, washed with brine, dried and the solvent was removed by evaporation. The product was isolated by chromatography on silica gel. The material was dissolved in dichloromethane (5 mL) and pTSA (5 mg) was added and heated to 50° C. for 3 hours. The misture was diluted with ethylacetate (20 mL), washed with 10% NaHCO3 (5 mL), brine (5 mL), dried with MgSO4 and the solvent was removed by evaporation to afford the title compound as an off. This mixture was added to a flask and stirred for 16 hours at ambient temperature The reaction was quenched by adding aq. NH4Cl the resulting mixture was extracted with ethylacetate washed with brine dried the solvent was removed by evaporation The product was isolated by chromatography on silica gel heated to 50° C. for 3 hours washed with 10% NaHCO3 (5 mL), brine (5 mL) dried with MgSO4 the solvent was removed by evaporation