3,4-dimethoxybenzenethiol

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:

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 a solution of 3,4-dimethoxythiophenol (8.25 mL, 57.6 mmol) in anhydrous THF (100 mL) at 0° C., is added n-BuLi (2.5 M in hexane, 0.77 mL, 1.92 mmol) and the solution is stirred for 15 minutes under a nitrogen atmosphere. t-butyl 7-phenyl-2-heptenoate (10 g, 38.4 mmol) in THF (100 mL) is added dropwise and the mixture is allowed to warm to room temperature and stir overnight. TLC analysis indicated complete reaction. The reaction mixture is diluted with water (300 mL) and extracted with ether (3×250 mL). Combined organic extracts are washed successively with sat. Na2CO3 solution (4×200 mL), water (200 mL) and brine (200 mL) then dried over MgSO4 and concentrated to afford a pale yellow oil which is chromatographed on silica gel (pet-ether/EtOAc, 9:1) to afford 14.9 g of (±)-t-butyl-3-(3,4-dimethoxyphenyl)sulfanyl-7-phenylheptanoate (90%) as a colorless oil. TLC analysis [pet-ether/EtOAc, 9:1, Rf (heptenoate)=0.80, Rf (heptanoate)=0.50]. 1H NMR (300 MHz, CDCl3) δ 1.44 (s, 9H), 1.48-1.68 (m, 6H), 2.42 (dABq, 2H), 2.60 (t, 2H), 3.28 (t, 1H), 3.85 (d, 6H), 6.75 (d, 1H), 7.0 (dd, 2H), 7.15 (d, 3H), 7.25 (t, 2H) ppm. Mass spectrum (FAB) m/z 447 (M+H)+. stir overnight reaction extracted with ether (3×250 mL) Combined organic extracts are washed successively with sat. Na2CO3 solution (4×200 mL), water (200 mL) and brine (200 mL) then dried over MgSO4 concentrated to afford a pale yellow oil which is chromatographed on silica gel (pet-ether/EtOAc, 9:1)

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

Procedure: To a solution of 3,4-dimethoxythiophenol (8.25 mL, 57.6 mmol) in anhydrous THF (100 mL) at 0° C., is added n-BuLi (2.5 M in hexane, 0.77 mL, 1.92 mmol) and the solution is stirred for 15 minutes under a nitrogen atmosphere. t-butyl 7-phenyl-2-heptenoate (10 g, 38.4 mmol) in THF (100 mL) is added dropwise and the mixture is allowed to warm to room temperature and stir overnight. TLC analysis indicated complete reaction. The reaction mixture is diluted with water (300 mL) and extracted with ether (3×250 mL). Combined organic extracts are washed successively with sat. Na2CO3 solution (4×200 mL), water (200 mL) and brine (200 mL) then dried over MgSO4 and concentrated to afford a pale yellow oil which is chromatographed on silica gel (pet-ether/EtOAc, 9:1) to afford 14.9 g of (±)-t-butyl-3-(3,4-dimethoxyphenyl)sulfanyl-7-phenylheptanoate (90%) as a colorless oil. TLC analysis [pet-ether/EtOAc, 9:1, Rf (heptenoate)=0.80, Rf (heptanoate)=0.50]. 1H NMR (300 MHz, CDCl3) δ 1.44 (s, 9H), 1.48-1.68 (m, 6H), 2.42 (dABq, 2H), 2.60 (t, 2H), 3.28 (t, 1H), 3.85 (d, 6H), 6.75 (d, 1H), 7.0 (dd, 2H), 7.15 (d, 3H), 7.25 (t, 2H) ppm. Mass spectrum (FAB) m/z 447 (M+H)+. stir overnight reaction extracted with ether (3×250 mL) Combined organic extracts are washed successively with sat. Na2CO3 solution (4×200 mL), water (200 mL) and brine (200 mL) then dried over MgSO4 concentrated to afford a pale yellow oil which is chromatographed on silica gel (pet-ether/EtOAc, 9:1)

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

Procedure: Sodium (0.5 g, 2.2 mmol) is added to MeOH (10 mL) cooled in ice. When the reaction is complete a solution of 3,4-dimethoxybenzenethiol (6 g, 3.5 mmol) in MeOH (5 mL) is added. After 2 minutes a solution of methyl 3-methanesulfonyloxy-2,2-dimethyl-7-phenylheptanoate (3 g, 8.8 mmol) in MeOH (5 mL) is added. The cooling bath is removed and the reaction is stirred at room temperature overnight. The solvent is removed in vacuo, CH2Cl2 (50 mL) added and the solution washed with NaHCO3 (50 mL), 1 N HCl (50 mL) and brine (50 mL). The solution is dried over MgSO4 and the solvent removed in vacuo. The product is purified by column chromatography (silica, 20% ether in petroleum ether) to yield methyl 3-(3,4-dimethoxyphenylsulfanyl)-2,2-dimethyl-7-phenylheptanoate (0.65 g, 18%): 1H NMR (300 MHz, CDCl3) δ 7.29-7.24 (m, 2H), 7.19-7.11 (m, 3H), 7.02-6.91 (m, 2H), 6.77 (d, J=8.2 Hz, 1H), 3,87 (s, 3H), 3.85 (s, 3H), 3.57 (s, 3H), 3.22 (dd, J=10.0, 3.2 Hz, 1H), 2.64-2.51 (m, 3H), 1.81-1.74 (m, 1H), 1.66-1.42 (m, 4H), 1.27 (s, 3H), 1.22 (s, 3H); MS (FAB) m/e 416 (M+). cooled in ice is added The cooling bath is removed The solvent is removed in vacuo, CH2Cl2 (50 mL) added the solution washed with NaHCO3 (50 mL), 1 N HCl (50 mL) and brine (50 mL) The solution is dried over MgSO4 the solvent removed in vacuo The product is purified by column chromatography (silica, 20% ether in petroleum ether)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-(4-Phenylbutyl)-2-oxaspiro[3,4]octan-1-one (2 g, 7.7 mmol) and 3,4-dimethoxybenzenethiol (2 g, 11.7 mmol) are dissolved in isopropanol (30 mL) and cooled to 0° C. A 1 M solution of NaOH (9.7 mL, 9.7 mmol) is added slowly, and after 5 minutes at 0° C., the reaction is allowed to stir at room temperature overnight. The solvent is removed in vacuo and the residue is dissolved in CH2Cl2 (100 mL). This solution is washed with 1 N HCl (50 mL), brine (30 mL) and dried over MgSO4. The solution is concentrated in vacuo and the crude product is purified by column chromatography (silica, 1% MeOH in CH2Cl2) to yield 1-[1-(3,4-dimethoxyphenylsulfanyl)-5-phenylpentyl]-cyclopentanecarboxylic acid (2.2 g, 65%). 1H NMR (300 MHz, CDCl3) δ 7.28-7.23 (m, 2H), 7.18-7.09 (m, 3H), 7.01-6.91 (m, 2H), 6.76 (d, J=8.1 Hz, 1H), 3.86 (s, 3H), 3.84 (s, 3H), 3.31 (dd, J=10.0, 3.0 Hz, 1H), 2.58-2.51 (m, 2H), 2.18-2.08 (m, 2H), 1.89-1.40 (m, 12H); MS (EI) m/e 428 (M+). The solvent is removed in vacuo the residue is dissolved in CH2Cl2 (100 mL) This solution is washed with 1 N HCl (50 mL), brine (30 mL) dried over MgSO4 The solution is concentrated in vacuo the crude product is purified by column chromatography (silica, 1% MeOH in CH2Cl2)

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 3-(4-Phenylbutyl)-2-oxaspiro[3,4]octan-1-one (2 g, 7.7 mmol) and 3,4-dimethoxybenzenethiol (2 g, 11.7 mmol) are dissolved in isopropanol (30 mL) and cooled to 0° C. A 1 M solution of NaOH (9.7 mL, 9.7 mmol) is added slowly, and after 5 minutes at 0° C., the reaction is allowed to stir at room temperature overnight. The solvent is removed in vacuo and the residue is dissolved in CH2Cl2 (100 mL). This solution is washed with 1 N HCl (50 mL), brine (30 mL) and dried over MgSO4. The solution is concentrated in vacuo and the crude product is purified by column chromatography (silica, 1% MeOH in CH2Cl2) to yield 1-[1-(3,4-dimethoxyphenylsulfanyl)-5-phenylpentyl]-cyclopentanecarboxylic acid (2.2 g, 65%). 1H NMR (300 MHz, CDCl3) δ 7.28-7.23 (m, 2H), 7.18-7.09 (m, 3H), 7.01-6.91 (m, 2H), 6.76 (d, J=8.1 Hz, 1H), 3.86 (s, 3H), 3.84 (s, 3H), 3.31 (dd, J=10.0, 3.0 Hz, 1H), 2.58-2.51 (m, 2H), 2.18-2.08 (m, 2H), 1.89-1.40 (m, 12H); MS (EI) m/e 428 (M+). The solvent is removed in vacuo the residue is dissolved in CH2Cl2 (100 mL) This solution is washed with 1 N HCl (50 mL), brine (30 mL) dried over MgSO4 The solution is concentrated in vacuo the crude product is purified by column chromatography (silica, 1% MeOH in CH2Cl2)