4-FLUORO-3-METHYLTHIOPHENOL

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Di-tert-butyl (1S,2R,5R,6R)-2-(tert-butoxycarbonylamino)-3-methylene-4-oxo-bicyclo[3.1.0]hexane-2,6-dicarboxylate (8 g, 18.9 mmol) in diethyl ether (80 mL) is bubbled with nitrogen gas for 10 minutes. 4-fluoro-3-methyl-benzenethiol (2.7 g, 18.9 mmol) and triethylamine (0.26 mL, 1.89 mmol) are added. The mixture is warmed to 40° C. and stirred for 15 minutes. The mixture is then allowed to cool to ambient temperature, transferred to addition funnel and added slowly over 2 hours to a 200 ml ether solution at −10° C. which contains S-(−)-2-methyl-CBS-oxazaborolidine (1M in tetrahydrofuran) (5.67 mL, 5.67 mmol) and borane-methyl sulfide complex (2M in tetrahydrofuran, 8.5 mL, 17 mmol). The mixture is stirred for an additional hour after final addition. Silica gel (40 g) is added over 30 minutes and the reaction mixture is gradually warmed to ambient temperature. The suspension is filtered, and washed with 300 ml of diethyl ether. The solvent is concentrated under reduced pressure giving a residue. The residue is purified by flash chromatography, eluting with (0 to 25% ethyl acetate/hexanes) to give the title compound (9.8 g, 17.3 mmol, 91.5% yield). MS (m/z): 565.8 (M−H). to cool to ambient temperature transferred to addition funnel The mixture is stirred for an additional hour after final addition Silica gel (40 g) is added over 30 minutes the reaction mixture is gradually warmed to ambient temperature The suspension is filtered washed with 300 ml of diethyl ether The solvent is concentrated under reduced pressure giving a residue The residue is purified by flash chromatography eluting with (0 to 25% ethyl acetate/hexanes)

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Di-tert-butyl (1S,2R,5R,6R)-2-(tert-butoxycarbonylamino)-3-methylene-4-oxo-bicyclo[3.1.0]hexane-2,6-dicarboxylate (8 g, 18.9 mmol) in diethyl ether (80 mL) is bubbled with nitrogen gas for 10 minutes. 4-fluoro-3-methyl-benzenethiol (2.7 g, 18.9 mmol) and triethylamine (0.26 mL, 1.89 mmol) are added. The mixture is warmed to 40° C. and stirred for 15 minutes. The mixture is then allowed to cool to ambient temperature, transferred to addition funnel and added slowly over 2 hours to a 200 ml ether solution at −10° C. which contains S-(−)-2-methyl-CBS-oxazaborolidine (1M in tetrahydrofuran) (5.67 mL, 5.67 mmol) and borane-methyl sulfide complex (2M in tetrahydrofuran, 8.5 mL, 17 mmol). The mixture is stirred for an additional hour after final addition. Silica gel (40 g) is added over 30 minutes and the reaction mixture is gradually warmed to ambient temperature. The suspension is filtered, and washed with 300 ml of diethyl ether. The solvent is concentrated under reduced pressure giving a residue. The residue is purified by flash chromatography, eluting with (0 to 25% ethyl acetate/hexanes) to give the title compound (9.8 g, 17.3 mmol, 91.5% yield). MS (m/z): 565.8 (M−H). to cool to ambient temperature transferred to addition funnel The mixture is stirred for an additional hour after final addition Silica gel (40 g) is added over 30 minutes the reaction mixture is gradually warmed to ambient temperature The suspension is filtered washed with 300 ml of diethyl ether The solvent is concentrated under reduced pressure giving a residue The residue is purified by flash chromatography eluting with (0 to 25% ethyl acetate/hexanes)

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: To a solution of 2-bromo-hexanoic acid methyl ester (0.500 g, 2.404 mmol) and 4-fluoro-3-methyl-benzenethiol (0.340 g, 2.404 mmol) in 20 mL of dichloromethane, was added triethylamine (3.3 mL, 12.020 mmol). After stirring at room temperature under N2 for 46 h, the reaction mixture was diluted with dichloromethane and washed with 1N HCl and brine. The organic layer dried over anhydrous Na2SO4. After removing the solvent under reduced pressure, the product was isolated by Flash chromatography (silica gel) eluting with 0-20% ethyl acetate/hexanes to give the title compound as colorless oil (0.596 g, 92% yield). LC-MS: tR=11.2 min; m/z 271 (M+H)+. washed with 1N HCl and brine The organic layer dried over anhydrous Na2SO4 After removing the solvent under reduced pressure the product was isolated by Flash chromatography (silica gel) eluting with 0-20% ethyl acetate/hexanes

反应条件: temp:40.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Di-tert-butyl (1S,2R,5R,6R)-2-(tert-butoxycarbonylamino)-3-methylene-4-oxo-bicyclo[3.1.0]hexane-2,6-dicarboxylate (8 g, 18.9 mmol) in diethyl ether (80 mL) is bubbled with nitrogen gas for 10 minutes. 4-fluoro-3-methyl-benzenethiol (2.7 g, 18.9 mmol) and triethylamine (0.26 mL, 1.89 mmol) are added. The mixture is warmed to 40° C. and stirred for 15 minutes. The mixture is then allowed to cool to ambient temperature, transferred to addition funnel and added slowly over 2 hours to a 200 ml ether solution at −10° C. which contains S-(−)-2-methyl-CBS-oxazaborolidine (1M in tetrahydrofuran) (5.67 mL, 5.67 mmol) and borane-methyl sulfide complex (2M in tetrahydrofuran, 8.5 mL, 17 mmol). The mixture is stirred for an additional hour after final addition. Silica gel (40 g) is added over 30 minutes and the reaction mixture is gradually warmed to ambient temperature. The suspension is filtered, and washed with 300 ml of diethyl ether. The solvent is concentrated under reduced pressure giving a residue. The residue is purified by flash chromatography, eluting with (0 to 25% ethyl acetate/hexanes) to give the title compound (9.8 g, 17.3 mmol, 91.5% yield). MS (m/z): 565.8 (M−H). to cool to ambient temperature transferred to addition funnel The mixture is stirred for an additional hour after final addition Silica gel (40 g) is added over 30 minutes the reaction mixture is gradually warmed to ambient temperature The suspension is filtered washed with 300 ml of diethyl ether The solvent is concentrated under reduced pressure giving a residue The residue is purified by flash chromatography eluting with (0 to 25% ethyl acetate/hexanes)