1-bromo-4-ethylsulfanylbenzene

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-Bromo-4-(ethylthio)benzene (16.0 g) in THF (80 ml) was added dropwise to magnesium (1.82 g) to maintain gentle reflux. The resulting cloudy solution was cooled to 0° and ethylene oxide (6.6 g) in THF (10 ml) was added dropwise. The mixture was stirred at room temperature for 30 min and at reflux for 1 h. Saturated aqueous ammonium chloride (200 ml) was added and the mixture was extracted with ER (2×200 ml). The dried extracted was evaporated and the residue was purified by [C] eluting with cyclohexane-ER (7.3) to give the title alcohol (2.15 g). T.l.c. (cyclohexane-ER 1:1) Rf 0.4. to maintain gentle reflux The resulting cloudy solution was cooled to 0° at reflux for 1 h the mixture was extracted with ER (2×200 ml) The dried extracted was evaporated the residue was purified by [C] eluting with cyclohexane-ER (7.3)

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-Bromo-4-ethylsulfanyl-benzene (5.0 g) was dissolved in acetic acid and potassium permanganate as a 3% solution in water (8 mL) was added. The reaction mixture was heated to 90° C. for 3 hrs, after which time the reaction was cooled to room temperature and partitioned between ethyl acetate and 2N NaOH solution (500 m) each. The organics were separated and washed with water (100 mL), dried over sodium sulfate and purified on biotage eluting with 90:10 hexanes : ethyl acetate to afford the title compound as a clear oil (2.70 g). 1H NMR (300 MHz, CDCl3): δ 1.30 (t, J=7.85 Hz, 3 H) 3.02 (q, J=7.54 Hz, 2 H), 7.40 (m, 4 H). after which time the reaction was cooled to room temperature partitioned between ethyl acetate and 2N NaOH solution (500 m) each The organics were separated washed with water (100 mL) dried over sodium sulfate purified on biotage eluting with 90:10 hexanes

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-Bromo-4-ethylsulfanyl-benzene (5.0 g) was dissolved in acetic acid and potassium permanganate as a 3% solution in water (8 mL) was added. The reaction mixture was heated to 90° C. for 3 hrs, after which time the reaction was cooled to room temperature and partitioned between ethyl acetate and 2N NaOH solution (500 m) each. The organics were separated and washed with water (100 mL), dried over sodium sulfate and purified on biotage eluting with 90:10 hexanes:ethyl acetate to afford the title compound as a clear oil (2.70 g). 1H NMR (300 MHz, CDCl3): δ 1.30 (t, J=7.85 Hz, 3 H) 3.02 (q, J=7.54 Hz, 2 H), 7.40 (m, 4 H). after which time the reaction was cooled to room temperature partitioned between ethyl acetate and 2N NaOH solution (500 m) each The organics were separated washed with water (100 mL) dried over sodium sulfate purified on biotage eluting with 90:10 hexanes

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-Bromo-4-ethylsulfanyl-benzene (5.0 g) was dissolved in acetic acid and potassium permanganate as a 3% solution in water (8 mL) was added. The reaction mixture was heated to 90° C. for 3 hrs, after which time the reaction was cooled to room temperature and partitioned between ethyl acetate and 2N NaOH solution (500 m) each. The organics were separated and washed with water (100 mL), dried over sodium sulfate and purified on biotage eluting with 90:10 hexanes:ethyl acetate to afford the title compound as a clear oil (2.70 g). 1H NMR (300 MHz, CDCl3): δ 1.30 (t, J=7.85 Hz, 3 H) 3.02 (q, J=7.54 Hz, 2 H), 7.40 (m, 4 H). after which time the reaction was cooled to room temperature partitioned between ethyl acetate and 2N NaOH solution (500 m) each The organics were separated washed with water (100 mL) dried over sodium sulfate purified on biotage eluting with 90:10 hexanes

Conditions: temp:65.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A Grignard reagent was prepared from 1-bromo-4-(ethylthio)benzene (1.1 g), magnesium (0.12 g), a catalytic amount of iodine and tetrahydrofuran (5 mL). To the Grignard reagent solution was added a solution of 2-(methoxymethoxy)-benzaldehyde (0.56 g) in tetrahydrofuran (12 mL), and the mixture was stirred at 65° C. for 10 minutes. After cooling to ambient temperature, a saturated aqueous ammonium chloride solution (5 mL) and water (20 mL) were added to the reaction mixture, and the mixture was extracted with ethyl acetate (80 mL). The extract was washed with water (20 mL) and brine (20 mL), dried over anhydrous sodium sulfate, then the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate=4/1) to give a diphenylmethanol compound (0.91 g). The obtained diphenylmethanol compound (0.90 g) was dissolved in dichloromethane (15 mL). To the solution was added a Dess-Martin reagent (1,1,1-tri(acetyloxy)-1,1-dihydro-1,2-benziodoxol-3(1H)-one) (1.5 g), and the mixture was stirred at 25° C. for 26 hours. To the reaction mixture were added diethyl ether (75 mL) and 1 mol/L aqueous sodium hydroxide solution (30 mL), the mixture was stirred vigorously, and the organic layer was separated. The organic layer was washed with 1 mol/L aqueous sodium hydroxide solution (30 mL), water (30 mL, 3 times) and brine (30 mL), dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate=15/1-9/1) to afford a ketone compound (0.82 g). A mixture of the obtained ketone compound (0.81 g), p-toluene-sulfonic acid monohydrate (0.10 g) and methanol (14 mL) was stirred at 60° C. for 4 hours. After cooling to ambient temperature, the reaction mixture was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate=15/1) to give a deprotected compound (0.69 g). The obtained deprotected compound (0.68 g) was dissolved in tetrahydrofuran (11 mL), triethylamine (0.41 mL) and methyl chloroformate (0.22 mL) were added to the solution, and the mixture was stirred at 25° C. for 1 hour. Furthermore, triethylamine (0.11 mL) and methyl chloroformate (0.061 mL) were added to the reaction mixture, and the mixture was stirred for 30 minutes. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was dissolved in tetrahydrofuran (14 mL) and water (7 mL), sodium borohydride (0.40 g) was added to the solution, and the mixture was stirred at 25° C. for 7 hours. To the reaction mixture was added dropwise 1 mol/L hydrochloric acid (15 mL), and the mixture was extracted with ethyl acetate (75 mL). The extract was washed with water (20 mL), a saturated aqueous sodium hydrogen carbonate solution (20 mL) and brine (20 mL), dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate=8/1) to give 2-(4-ethylthiobenzyl)phenol (0.62 g). After cooling to ambient temperature the mixture was extracted with ethyl acetate (80 mL) The extract was washed with water (20 mL) and brine (20 mL) dried over anhydrous sodium sulfate the solvent was removed under reduced pressure The residue was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate=4/1)

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

Procedure: A Grignard reagent was prepared from 1-bromo-4-(ethylthio)benzene (1.1 g), magnesium (0.12 g), a catalytic amount of iodine and tetrahydrofuran (5 mL). To the Grignard reagent solution was added a solution of 2-(methoxymethoxy)-benzaldehyde (0.56 g) in tetrahydrofuran (12 mL), and the mixture was stirred at 65% for 10 minutes. After cooling to ambient temperature, a saturated aqueous ammonium chloride solution (5 mL) and water (20 mL) were added to the reaction mixture, and the mixture was extracted with ethyl acetate (80 mL). The extract was washed with water (20 mL) and brine (20 mL), dried over anhydrous sodium sulfate, then the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate=4/1) to give a diphenylmethanol compound (0.91 g). The obtained diphenylmethanol compound (0.90 g) was dissolved in dichloromethane (15 mL). To the solution was added a Dess-Martin reagent (1,1,1-tri(acetyloxy)-1,1-dihydro-1,2-benziodoxol-3(1H)-one) (1.5 g), and the mixture was stirred at 25° C. for 26 hours. To the reaction mixture were added diethyl ether (75 mL) and 1 mol/L aqueous sodium hydroxide solution (30 mL), the mixture was stirred vigorously, and the organic layer was separated. The organic layer was washed with 1 mol/L aqueous sodium hydroxide solution (30 mL), water (30 mL, 3 times) and brine (30 mL), dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate=15/1–9/1) to afford a ketone compound (0.82 g). A mixture of the obtained ketone compound (0.81 g), p-toluene-sulfonic acid monohydrate (0.10 g) and methanol (14 mL) was stirred at 60° C. for 4 hours. After cooling to ambient temperature, the reaction mixture was concentrated under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate=15/1) to give a deprotected compound (0.69 g). The obtained deprotected compound (0.68 g) was dissolved in tetrahydrofuran (11 mL), triethylamine (0.41 mL) and methyl chloroformate (0.22 mL) were added to the solution, and the mixture was stirred at 25° C. for 1 hour. Furthermore, triethylamine (0.11 mL) and methyl chloroformate (0.061 mL) were added to the reaction mixture, and the mixture was stirred for 30 minutes. The reaction mixture was filtered, and the filtrate was concentrated under reduced pressure. The residue was dissolved in tetrahydrofuran (14 mL) and water (7 mL), sodium borohydride (0.40 g) was added to the solution, and the mixture was stirred at 25° C. for 7 hours. To the reaction mixture was added dropwise 1 mol/L hydrochloric acid (15 mL), and the mixture was extracted with ethyl acetate (75 mL). The extract was washed with water (20 mL), a saturated aqueous sodium hydrogen carbonate solution (20 mL) and brine (20 mL), dried over anhydrous sodium sulfate, and the solvent was removed under reduced pressure. The residue was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate=8/1) to give 2-(4-ethylthiobenzyl)phenol (0.62 g). the mixture was extracted with ethyl acetate (80 mL) The extract was washed with water (20 mL) and brine (20 mL) dried over anhydrous sodium sulfate the solvent was removed under reduced pressure The residue was purified by column chromatography on silica gel (eluent: hexane/ethyl acetate=4/1)

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

Procedure: 1-Bromo-4-(ethylthio)benzene (0.5 g, 2.3 mmol) was added to a stirred mixture of magnesium turnings (1.96 g, 82 mmol) in THF (10 mL). 1,2-Dibromoethane (30 μL) was then added and the mixture was heated at reflux to initiate the reaction. A solution of 1-bromo-4-(ethylthio)benzene (18.2 g, 84 mmol) in THF (60 mL) was added at such a rate to maintain the reaction mixture at gentle reflux. The reaction mixture was then stirred at 50° C. for 90 min and cooled to ambient temp to give a 1.16M solution of 4-(ethylthio)phenylmagnesium bromide in THF which was used in the next reaction. the mixture was heated at reflux the reaction to maintain the reaction mixture at gentle reflux cooled to ambient temp

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-Bromo-4-ethylsulfanyl-benzene (5.0 g) was dissolved in acetic acid and potassium permanganate as a 3% solution in water (8 mL) was added. The reaction mixture was heated to 90° C. for 3 hrs, after which time the reaction was cooled to room temperature and partitioned between ethyl acetate and 2N NaOH solution (500 m) each. The organics were separated and washed with water (100 mL), dried over sodium sulfate and purified on biotage eluting with 90:10 hexanes:ethyl acetate to afford the title compound as a clear oil (2.70 g). 1H NMR (300 MHz, CDCl3): δ 1.30 (t, J=7.85 Hz, 3H) 3.02 (q, J=7.54 Hz, 2H), 7.40 (m, 4H). after which time the reaction was cooled to room temperature partitioned between ethyl acetate and 2N NaOH solution (500 m) each The organics were separated washed with water (100 mL) dried over sodium sulfate purified on biotage eluting with 90:10 hexanes

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

Procedure: 1-Bromo-4-(ethylthio)benzene (16.0 g) in THF (80 ml) was added dropwise to magnesium (1.82 g) to maintain gentle reflux. The resulting cloudy solution was cooled to 0° and ethylene oxide (6.6 g) in THF (10 ml) was added dropwise. The mixture was stirred at room temperature for 30 min and at reflux for 1 h. Saturated aqueous ammonium chloride (200 ml) was added and the mixture was extracted with ER (2×200 ml). The dried extracted was evaporated and the residue was purified by [C] eluting with cyclohexane-ER (7.3) to give the title alcohol (2.15 g). T.l.c. (cyclohexane-ER 1:1) Rf 0.4. to maintain gentle reflux The resulting cloudy solution was cooled to 0° at reflux for 1 h the mixture was extracted with ER (2×200 ml) The dried extracted was evaporated the residue was purified by [C] eluting with cyclohexane-ER (7.3)

Conditions: temp:90.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1-Bromo-4-ethylsulfanyl-benzene (5.0 g) was dissolved in acetic acid and potassium permanganate as a 3% solution in water (8 mL) was added. The reaction mixture was heated to 90° C. for 3 hrs, after which time the reaction was cooled to room temperature and partitioned between ethyl acetate and 2N NaOH solution (500 m) each. The organics were separated and washed with water (100 mL), dried over sodium sulfate and purified on biotage eluting with 90:10 hexanes : ethyl acetate to afford the title compound as a clear oil (2.70 g). 1H NMR (300 MHz, CDCl3): δ 1.30 (t, J=7.85 Hz, 3 H) 3.02 (q, J=7.54 Hz, 2 H), 7.40 (m, 4 H). after which time the reaction was cooled to room temperature partitioned between ethyl acetate and 2N NaOH solution (500 m) each The organics were separated washed with water (100 mL) dried over sodium sulfate purified on biotage eluting with 90:10 hexanes