ethyl 2-methyl-3-sulfanylpropanoate

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: At -40° C., Et3N (triethylamine) (1.60 mL, 11.5 mmol) and methanesulfonyl chloride (750 μl, 9.69 mmol) were added to a solution of the alcohol of Step 6 (7.39 mmol) in 74 mL of CH2Cl2 and the mixture was stirred at -40° C. for an hour and at -10° C. for 45 minutes. Saturated aq NaHCO3 was then added and the mesylate was extracted with CH2Cl2, dried over Na2SO4 and concentrated. To this mesylate in 150 mL of anhydrous CH3CN, ethyl 3-mercapto-2-methylpropanoate (Example 4, Step 6; 2.20 mL, approx. 15 mmol) and Cs2CO3 (7.57 g, 23.2 mmol) were added and the mixture was stirred under a stream of N2 for 2 hours. 25% Aq NH4OAc was then added and the title product was extracted with EtOAc, dried over Na2SO4 and purified by flash chromatography on silica with EtOAc:toluene. the mesylate was extracted with CH2Cl2 dried over Na2SO4 concentrated the title product was extracted with EtOAc dried over Na2SO4 purified by flash chromatography on silica with EtOAc

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To the crude chloride of Step 4 dissolved in 10 mL of DNE, ethyl 3-mercapto-2-methylpropanoate (Step 6; 350 μl, approx. 2.4 mmol) and Cs2CO3 (1.61 g, 4.9 mmol) were added and the mixture was stirred at r.t. for 3.5 h. 25% Aq NH4OAc was then added and the reaction mixture was extracted with EtOAc, dried over Na2SO4 and purified by flash chromatography on silica using EtOAc:toluene 7.5:92.5 and 10:90 to yield 347 mg of the title compound as an oil (52% yield for Steps 6 and 7). were added the reaction mixture was extracted with EtOAc dried over Na2SO4 purified by flash chromatography on silica

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: At -20° C., 3N NaOH (150 mL, 450 mmol) was added dropwise to a solution of ethyl 3-(acetylthio)-2-methylpropanoate (66.47 g, 349 mmol, Step 5) in 700 mL of MeOH and the mixture was stirred at that temperature for 30 min. 25% Ag NH4OAc was then added and the title thiol was extracted with EtOAc, dried over MgSO4, concentrated and distilled to yield 42.52 g (82%) of the title compound as an oil; bp: 96°-98° C./15 mm Hg. the title thiol was extracted with EtOAc dried over MgSO4 concentrated distilled

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: At -40° C., Et3N (triethylamine) (1.60 mL, 11.5 mmol) and methanesulfonyl chloride (750 μl, 9.69 mmol) were added to a solution of the alcohol of Step 6 (7.39 mmol) in 74 mL of CH2Cl2 and the mixture was stirred at -40° C. for an hour and at -10° C. for 45 minutes. Saturated aq NaHCO3 was then added and the mesylate was extracted with CH2Cl2, dried over Na2SO4 and concentrated. To this mesylate in 150 mL of anhydrous CH3CN, ethyl 3-mercapto-2-methylpropanoate (Example 4, Step 6; 2.20 mL, approx. 15 mmol) and Cs2CO3 (7.57 g, 23.2 mmol) were added and the mixture was stirred under a stream of N2 for 2 hours. 25% Aq NH4OAc was then added and the title product was extracted with EtOAc, dried over Na2SO4 and purified by flash chromatography on silica with EtOAc:toluene. the mesylate was extracted with CH2Cl2 dried over Na2SO4 concentrated the title product was extracted with EtOAc dried over Na2SO4 purified by flash chromatography on silica with EtOAc

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To the crude chloride of Step 4 dissolved in 10 mL of DMF, ethyl 3-mercapto-2-methylpropanoate (Step 6; 350 μl, approx. 2.4 mmol) and Cs2CO3 (1.61 g, 4.9 mmol) were added and the mixture was stirred at r.t. for 3.5 h. 25% Aq NH4OAc was then added and the reaction mixture was extracted with EtOAc, dried over Na2SO4 and purified by flash chromatography on silica using EtOAc:toluene 7.5:92.5 and 10:90 to yield 347 mg of the title compound as an oil (52% yield for Steps 6 and 7). the reaction mixture was extracted with EtOAc dried over Na2SO4 purified by flash chromatography on silica

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: At -20° C., 3N NaOH (150 mL, 450 mmol) was added dropwise to a solution of ethyl 3-(acetylthio)-2-methylpropanoate (66.47 g, 349 mmol, Step 5) in 700 mL of MeOH and the mixture was stirred at that temperature for 30 min. 25% Aq NH4OAc was then added and the title thiol was extracted with EtOAc, dried over MgSO4, concentrated and distilled to yield 42.52 g (82%) of the title compound as an oil; bp: 96°-98° C./15 mm Hg. the title thiol was extracted with EtOAc dried over MgSO4 concentrated distilled

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: At -20° C., 3N NaOH (150 mL, 450 mmol) was added dropwise to a solution of ethyl 3-(acetylthio)-2-methylpropanoate (66.47 g, 349 mmol, obtained from ethyl methacrylate as in Example 10, Step 1) in 700 mL of MeOH and the mixture was stirred at that temperature for 30 min. 25% Aq NH4OAc was then added and the title thiol was extracted with EtOAc, dried over MgSO4, concentrated and distilled to yield 42.52 g (82%) of the title compound as an oil; bp: 96°-98° C./15 mm Hg. the title thiol was extracted with EtOAc dried over MgSO4 concentrated distilled

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: At -20° C., 3N NaOH (150 mL, 450 mmol) was added dropwise to a solution of ethyl 3-(acetylthio)-2-methylpropanoate (66.47 g, 349 mmol, obtained from ethyl methacrylate as in Example 10, Step 1) in 700 mL of MeOH and the mixture was stirred at that temperature for 30 min. 25% Aq NH4OAc was then added and the title thiol was extracted with EtOAc, dried over MgSO4, concentrated and distilled to yield 42.52 g (82%) of the title compound as an oil; bp: 96°-98° C./15 mm Hg. the title thiol was extracted with EtOAc dried over MgSO4 concentrated distilled

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: At -10° C., AlCl3 (2.437 g, 18.3 mmol) was added to a solution of the styrene of Step 7 (1.013 g, 2.28 mmol) and 3-mercapto-2-methylpropanoic acid (356 mg, 2.96 mmol, obtained from the hydrolysis of ethyl 3-mercapto-2-methylpropanoate (Example 1, Method B, Step 6) as in Example 7, Step 4, or alternatively from the NaOH hydrolysis of ethyl 3-(acetylthio)-2-methylpropanoate) in 25 mL of CH2Cl2 and the mixture was stirred at 0° C. in the dark for 2 h. Cold aq NH4OAc, EtOAc and THF were then added and the mixture was stirred until complete dissolution of the oil. The product was extracted with EtOAc:THF 1:1, dried over Na2SO4 and concentrated. The sodium salt of the acid was formed in EtOH with 500 μl of 10N NaOH. It was purified on an Amberlite ion exchange resin XAD-8: elution with water separate the sodium 3-mercapto-2-methyl-propanoate and elution with methanol afforded the title acid as an impure sodium salt. The compound was dissolved in saturated aq NH4Cl, extracted with EtOAc:THF 1:1, dried over Na2SO4 and purified by flash chromatography on silica using acetone:toluene:acetic acid 5:95:1 to yield 766 mg (60%) of the title acid.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: At -10° C., AlCl3 (2.437 g, 18.3 mmol) was added to a solution of the styrene of Step 7 (1.013 g, 2.28 mmol) and 3-mercapto-2-methylpropanoic acid (356 mg, 2.96 mmol, obtained from the hydrolysis of ethyl 3-mercapto-2-methylpropanoate (Example 1, Method B, Step 6) as in Example 7, Step 4, or alternatively from the NaOH hydrolysis of ethyl 3-(acetylthio)-2-methylpropanoate) in 25 mL of CH2Cl2 and the mixture was stirred at 0° C. in the dark for 2 h. Cold aq NH4OAc, EtOAc and THF were then added and the mixture was stirred until complete dissolution of the oil. The product was extracted with EtOAc:THF 1:1, dried over Na2SO4 and concentrated. The sodium salt of the acid was formed in EtOH with 500 μl of 10N NaOH. It was purified on an Amberlite ion exchange resin XAD-8: elution with water separate the sodium 3-mercapto-2-methyl-propanoate and elution with methanol afforded the title acid as an impure sodium salt. The compound was dissolved in saturated aq NH4Cl, extracted with EtOAc:THF 1:1, dried over Na2SO4 and purified by flash chromatography on silica using acetone:toluene:acetic acid 5:95:1 to yield 766 mg (60%) of the title acid.

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: At -40° C., Et3N (triethylamine) (1.60 mL, 11.5 mmol) and methanesulfonyl chloride (750 μl, 9.69 mmol) were added to a solution of the alcohol of Step 6 (7.39 mmol) in 74 mL of CH2Cl2 and the mixture was stirred at -40° C. for an hour and at -10° C. for 45 minutes. Saturated aq NaHCO3 was then added and the mesylate was extracted with CH2Cl2, dried over Na2SO4 and concentrated. To this mesylate in 150 mL of anhydrous CH3CN, ethyl 3-mercapto-2-methylpropanoate (Example 4, Step 6; 2.20 mL, approx. 15 mmol) and Cs2CO3 (7.57 g, 23.2 mmol) were added and the mixture was stirred under a stream of N2 for 2 hours. 25% Aq NH4OAc was then added and the title product was extracted with EtOAc, dried over Na2SO4 and purified by flash chromatography on silica with EtOAc:toluene. the mesylate was extracted with CH2Cl2 dried over Na2SO4 concentrated the title product was extracted with EtOAc dried over Na2SO4 purified by flash chromatography on silica with EtOAc

反応条件: temp:-10.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: At -40° C., Et3N (triethylamine) (1.60 mL, 11.5 mmol) and methanesulfonyl chloride (750 μl, 9.69 mmol) were added to a solution of the alcohol of Step 6 (7.39 mmol) in 74 mL of CH2Cl2 and the mixture was stirred at -40° C. for an hour and at -10° C. for 45 minutes. Saturated aq NaHCO3 was then added and the mesylate was extracted with CH2Cl2, dried over Na2SO4 and concentrated. To this mesylate in 150 mL of anhydrous CH3CN, ethyl 3-mercapto-2-methylpropanoate (Example 4, Step 6; 2.20 mL, approx. 15 mmol) and Cs2CO3 (7.57 g, 23.2 mmol) were added and the mixture was stirred under a stream of N2 for 2 hours. 25% Aq NH4OAc was then added and the title product was extracted with EtOAc, dried over Na2SO4 and purified by flash chromatography on silica with EtOAc:toluene. the mesylate was extracted with CH2Cl2 dried over Na2SO4 concentrated the title product was extracted with EtOAc dried over Na2SO4 purified by flash chromatography on silica with EtOAc