ethyl 1,3-dithiolane-2-carboxylate

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

Procedure: 83 ml. of 1.65M. n-butyllithium/hexane (138 mmoles) is added via syringe to a solution of 20.2 ml. (14.58 g.; 144 mmoles) of diisopropylamine in 200 ml. of dry tetrahydrofuran (distilled from ketyl) stirred at -78° C., the reaction mixture is warmed to 0° C. and cooled to -78° C., 18.7 ml. (23.35 g.; 131 mmoles) of ethyl 1,3-dithiolane-2-carboxylate (Compound CV) is added dropwise to the reaction mixture stirred at -78° C., the reaction mixture is stirred at -78° C. for 30 minutes, a solution of 22.749 g. (131 mmoles) of Compound CIV in 50 ml. of dry tetrahydrofuran (distilled from ketyl) is added dropwise with stirring at -78° C., and the reaction mixture is stirred at -78° C. for 3 hours, the reaction mixture being maintained under dry nitrogen throughout. The reaction mixture is quenched at -78° C. with saturated ammonium chloride solution and warmed to 20°-25° C., the tetrahydrofuran is evaporated at reduced pressure, and the residue is partitioned between ethyl acetate and water. The aqueous phase is acidified to about pH 2 with 10% hydrochloric acid and extracted with ethyl acetate. The ethyl acetate layers are combined, washed twice with saturated sodium chloride solution, dried over anhydrous magnesium sulfate, filtered and evaporated at reduced pressure. The residue is triturated with diethyl ether to obtain the crude product as a white solid (27.13 g.). cooled to -78° C. the reaction mixture is stirred at -78° C. for 30 minutes with stirring at -78° C. the reaction mixture is stirred at -78° C. for 3 hours the reaction mixture being maintained under dry nitrogen throughout The reaction mixture is quenched at -78° C. with saturated ammonium chloride solution warmed to 20°-25° C. the tetrahydrofuran is evaporated at reduced pressure the residue is partitioned between ethyl acetate and water extracted with ethyl acetate washed twice with saturated sodium chloride solution dried over anhydrous magnesium sulfate filtered evaporated at reduced pressure The residue is triturated with diethyl ether

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

Procedure: 83 ml. of 1.65M. n-butyllithium/hexane (138 mmoles) is added via syringe to a solution of 20.2 ml. (14.58 g.; 144 mmoles) of diisopropylamine in 200 ml. of dry tetrahydrofuran (distilled from ketyl) stirred at -78° C., the reaction mixture is warmed to 0° C. and cooled to -78° C., 18.7 ml. (23.35 g.; 131 mmoles) of ethyl 1,3-dithiolane-2-carboxylate (Compound CV) is added dropwise to the reaction mixture stirred at -78° C., the reaction mixture is stirred at -78° C. for 30 minutes, a solution of 22.749 g. (131 mmoles) of Compound CIV in 50 ml. of dry tetrahydrofuran (distilled from ketyl) is added dropwise with stirring at -78° C., and the reaction mixture is stirred at -78° C. for 3 hours, the reaction mixture being maintained under dry nitrogen throughout. The reaction mixture is quenched at -78° C. with saturated ammonium chloride solution and warmed to 20°-25° C., the tetrahydrofuran is evaporated at reduced pressure, and the residue is partitioned between ethyl acetate and water. The aqueous phase is acidified to about pH 2 with 10% hydrochloric acid and extracted with ethyl acetate. The ethyl acetate layers are combined, washed twice with saturated sodium chloride solution, dried over anhydrous magnesium sulfate, filtered and evaporated at reduced pressure. The residue is triturated with diethyl ether to obtain the crude product as a white solid (27.13 g.). cooled to -78° C. the reaction mixture is stirred at -78° C. for 30 minutes with stirring at -78° C. the reaction mixture is stirred at -78° C. for 3 hours the reaction mixture being maintained under dry nitrogen throughout The reaction mixture is quenched at -78° C. with saturated ammonium chloride solution warmed to 20°-25° C. the tetrahydrofuran is evaporated at reduced pressure the residue is partitioned between ethyl acetate and water extracted with ethyl acetate washed twice with saturated sodium chloride solution dried over anhydrous magnesium sulfate filtered evaporated at reduced pressure The residue is triturated with diethyl ether

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

Procedure: 83 ml. of 1.65M. n-butyllithium/hexane (138 mmoles) is added via syringe to a solution of 20.2 ml. (14.58 g.; 144 mmoles) of diisopropylamine in 200 ml. of dry tetrahydrofuran (distilled from ketyl) stirred at -78° C., the reaction mixture is warmed to 0° C. and cooled to -78° C., 18.7 ml. (23.35 g.; 131 mmoles) of ethyl 1,3-dithiolane-2-carboxylate (Compound CV) is added dropwise to the reaction mixture stirred at -78° C., the reaction mixture is stirred at -78° C. for 30 minutes, a solution of 22.749 g. (131 mmoles) of Compound CIV in 50 ml. of dry tetrahydrofuran (distilled from ketyl) is added dropwise with stirring at -78° C., and the reaction mixture is stirred at -78° C. for 3 hours, the reaction mixture being maintained under dry nitrogen throughout. The reaction mixture is quenched at -78° C. with saturated ammonium chloride solution and warmed to 20°-25° C., the tetrahydrofuran is evaporated at reduced pressure, and the residue is partitioned between ethyl acetate and water. The aqueous phase is acidified to about pH 2 with 10% hydrochloric acid and extracted with ethyl acetate. The ethyl acetate layers are combined, washed twice with saturated sodium chloride solution, dried over anhydrous magnesium sulfate, filtered and evaporated at reduced pressure. The residue is triturated with diethyl ether to obtain the crude product as a white solid (27.13 g.). cooled to -78° C. the reaction mixture is stirred at -78° C. for 30 minutes with stirring at -78° C. the reaction mixture is stirred at -78° C. for 3 hours the reaction mixture being maintained under dry nitrogen throughout The reaction mixture is quenched at -78° C. with saturated ammonium chloride solution warmed to 20°-25° C. the tetrahydrofuran is evaporated at reduced pressure the residue is partitioned between ethyl acetate and water extracted with ethyl acetate washed twice with saturated sodium chloride solution dried over anhydrous magnesium sulfate filtered evaporated at reduced pressure The residue is triturated with diethyl ether

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A vigorously stirred slurry of ethyl 1,3-dithiolane-2-carboxylate (8, 1.50 mL, 10.5 mmol) and N,O-dimethylhydroxylamine hydrochloride (2.57 g, 26.2 mmol) in THF (21 mL) was treated dropwise with isopropylmagnesium bromide (52.5 mmol, 26.3 mL, 2 M in THF) over 40 min at −78° C. under argon. The reaction mixture was stirred for 1 h at −78° C. under argon. The reaction mixture was quenched with saturated aqueous NH4Cl/H2O (1:1). The aqueous phase was extracted with ether (3×100 mL). The combined organic extract was washed (water, brine), dried (Na2SO4), concentrated and chromatographed [silica, EtOAc/hexanes (2:1)] to afford a yellow oil that solidified upon storage at 1° C. (985 mg, 49%). The characterization values (1H NMR, 13C NMR, ESI-MS) were consistent with those for the title compound prepared via a different synthetic route.43 The reaction mixture was quenched with saturated aqueous NH4Cl/H2O (1:1) The aqueous phase was extracted with ether (3×100 mL) The combined organic extract was washed (water, brine) dried (Na2SO4) concentrated chromatographed [silica, EtOAc/hexanes (2:1)] to afford a yellow oil that solidified upon storage at 1° C.

Conditions: temp:-78.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: n-Butyllithium (6.5 mL, 1.6 M in hexane) was added to a solution of ethyl 1,3-dithiolane-2-carboxylate (1925 mg, 10 mmol) in THF (10 mL) at −78° C. under N2. The reaction mixture was stirred for 30 min at −78° C. and then 4-bromobutanenitrile (1469 mg, 10 mmol) in THE (10 mL) was added. The mixture was warmed to room temperature and stirred for 30 min. It was diluted with diethyl ether and washed with 1 N HCl and H2O, and dried. Evaporation and purification by column chromatography afforded ethyl 2-(3-cyanopropyl)-1,3-dithiolane-2-carboxylate: LCMS tR=1.86 Min (5 min run, UV254nm), Mass calculated for, M+259.0, observed LC/MS m/z 260.0 (M+H). The mixture was warmed to room temperature stirred for 30 min washed with 1 N HCl and H2O dried Evaporation and purification by column chromatography

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

Procedure: 83 ml. of 1.65M. n-butyllithium/hexane (138 mmoles) is added via syringe to a solution of 20.2 ml. (14.58 g.; 144 mmoles) of diisopropylamine in 200 ml. of dry tetrahydrofuran (distilled from ketyl) stirred at -78° C., the reaction mixture is warmed to 0° C. and cooled to -78° C., 18.7 ml. (23.35 g.; 131 mmoles) of ethyl 1,3-dithiolane-2-carboxylate (Compound CV) is added dropwise to the reaction mixture stirred at -78° C., the reaction mixture is stirred at -78° C. for 30 minutes, a solution of 22.749 g. (131 mmoles) of Compound CIV in 50 ml. of dry tetrahydrofuran (distilled from ketyl) is added dropwise with stirring at -78° C., and the reaction mixture is stirred at -78° C. for 3 hours, the reaction mixture being maintained under dry nitrogen throughout. The reaction mixture is quenched at -78° C. with saturated ammonium chloride solution and warmed to 20°-25° C., the tetrahydrofuran is evaporated at reduced pressure, and the residue is partitioned between ethyl acetate and water. The aqueous phase is acidified to about pH 2 with 10% hydrochloric acid and extracted with ethyl acetate. The ethyl acetate layers are combined, washed twice with saturated sodium chloride solution, dried over anhydrous magnesium sulfate, filtered and evaporated at reduced pressure. The residue is triturated with diethyl ether to obtain the crude product as a white solid (27.13 g.). cooled to -78° C. the reaction mixture is stirred at -78° C. for 30 minutes with stirring at -78° C. the reaction mixture is stirred at -78° C. for 3 hours the reaction mixture being maintained under dry nitrogen throughout The reaction mixture is quenched at -78° C. with saturated ammonium chloride solution warmed to 20°-25° C. the tetrahydrofuran is evaporated at reduced pressure the residue is partitioned between ethyl acetate and water extracted with ethyl acetate washed twice with saturated sodium chloride solution dried over anhydrous magnesium sulfate filtered evaporated at reduced pressure The residue is triturated with diethyl ether

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

Procedure: 83 ml. of 1.65M. n-butyllithium/hexane (138 mmoles) is added via syringe to a solution of 20.2 ml. (14.58 g.; 144 mmoles) of diisopropylamine in 200 ml. of dry tetrahydrofuran (distilled from ketyl) stirred at -78° C., the reaction mixture is warmed to 0° C. and cooled to -78° C., 18.7 ml. (23.35 g.; 131 mmoles) of ethyl 1,3-dithiolane-2-carboxylate (Compound CV) is added dropwise to the reaction mixture stirred at -78° C., the reaction mixture is stirred at -78° C. for 30 minutes, a solution of 22.749 g. (131 mmoles) of Compound CIV in 50 ml. of dry tetrahydrofuran (distilled from ketyl) is added dropwise with stirring at -78° C., and the reaction mixture is stirred at -78° C. for 3 hours, the reaction mixture being maintained under dry nitrogen throughout. The reaction mixture is quenched at -78° C. with saturated ammonium chloride solution and warmed to 20°-25° C., the tetrahydrofuran is evaporated at reduced pressure, and the residue is partitioned between ethyl acetate and water. The aqueous phase is acidified to about pH 2 with 10% hydrochloric acid and extracted with ethyl acetate. The ethyl acetate layers are combined, washed twice with saturated sodium chloride solution, dried over anhydrous magnesium sulfate, filtered and evaporated at reduced pressure. The residue is triturated with diethyl ether to obtain the crude product as a white solid (27.13 g.). cooled to -78° C. the reaction mixture is stirred at -78° C. for 30 minutes with stirring at -78° C. the reaction mixture is stirred at -78° C. for 3 hours the reaction mixture being maintained under dry nitrogen throughout The reaction mixture is quenched at -78° C. with saturated ammonium chloride solution warmed to 20°-25° C. the tetrahydrofuran is evaporated at reduced pressure the residue is partitioned between ethyl acetate and water extracted with ethyl acetate washed twice with saturated sodium chloride solution dried over anhydrous magnesium sulfate filtered evaporated at reduced pressure The residue is triturated with diethyl ether