ethyl 2-(cyclopropylmethyl)-1,3-dithiane-2-carboxylate

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: A solution of ethyl 2-(cyclopropylmethyl)-1,3-dithiane-2-carboxylate (19.6 g, 79.67 mmol) in CH3CN (20 mL) was slowly added, over 30 minutes, to a well-stirred suspension of NBS (N-bromosuccinimide) in CH3CN (210 mL) and water (55 mL). After the mixture was stirred for 1 h, the resulting red solution was poured into an ice-cold CH2Cl2-Hexane solution (1:1 500 mL). The resulting mixture was washed with saturated aqueous NaHSO3 and water. The colorless organic phase was carefully washed with saturated aqueous K2CO3 and water. The organic phase was dried over MgSO4, then evaporated to give 6.88 g (55%) of ethyl 3-cyclopropyl-2-oxopropanoate as a yellow oil. 1H NMR (CDCl3): δ 4.29 (2H, q, J=8 Hz), 2.71 (2H, d, J=9 Hz), 1.35 (3H, t, J=8 Hz), 1.05-0.98 (1H, m), 0.59-0.54 (2H, m), 0.17-0.14 (2H, m). The resulting mixture was washed with saturated aqueous NaHSO3 and water The colorless organic phase was carefully washed with saturated aqueous K2CO3 and water The organic phase was dried over MgSO4 evaporated

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

実験手順: A solution of ethyl 2-(cyclopropylmethyl)-1,3-dithiane-2-carboxylate (19.6 g, 79.67 mmol) in CH3CN (20 mL) was slowly added, over 30 minutes, to a well-stirred suspension of NBS (N-bromosuccinimide) in CH3CN (210 mL) and water (55 mL). After the mixture was stirred for 1 h, the resulting red solution was poured into an ice-cold CH2Cl2-Hexane solution (1:1 500 mL). The resulting mixture was washed with saturated aqueous NaHSO3 and water. The colorless organic phase was carefully washed with saturated aqueous K2CO3 and water. The organic phase was dried over MgSO4, then evaporated to give 6.88 g (55%) of ethyl 3-cyclopropyl-2-oxopropanoate as a yellow oil. 1H NMR (CDCl3): δ 4.29 (2H, q, J=8 Hz), 2.71 (2H, d, J=9 Hz), 1.35 (3H, t, J=8 Hz), 1.05-0.98 (1H, m), 0.59-0.54 (2H, m), 0.17-0.14 (2H, m). The resulting mixture was washed with saturated aqueous NaHSO3 and water The colorless organic phase was carefully washed with saturated aqueous K2CO3 and water The organic phase was dried over MgSO4 evaporated

反応条件: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a suspension of NaH (95%, 2.8 g, 111 mmol) in dry toluene (120 mL) stirring at 0° C. was dropwise added, over 10 minutes, a solution of bromomethylcyclopropane (15 g, 111 mmol), and ethyl 1,3-dithiane-2-carboxylate (17.77 g, 92.58 mmol) in dry DMF (40 mL). The ice bath was removed and the solution was stirred overnight at rt. Water was added to the solution and the phases were separated. The organic phase was dried over MgSO4, then evaporated to give 19.6 g (50%) of ethyl 2-(cyclopropylmethyl)-1,3-dithiane-2-carboxylate, which was used in the next step without purification. 1H NMR (CDCl3): δ 4.26 (2H, q, J=7.2 Hz), 3.30-3.23 (2H, m), 2.69-2.64 (2H, m), 2.16-2.11 (1H, m), 1.96 (2H, d, J=6.8 Hz), 1.91-1.81 (1H, m), 1.34 (3H, t, J=7.2 Hz), 0.93-0.86 (1H, m), 0.52-0.47 (2H, m), 0.20-0.16 (2H, m). was dropwise added, over 10 minutes The ice bath was removed the solution was stirred overnight at rt Water was added to the solution the phases were separated The organic phase was dried over MgSO4 evaporated

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

反応条件: temp:0.00; pressure:0.00; stir:

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

実験手順: To a 0° C. suspension of NBS (439 mmol, 79 g) in a mixture of acetonitrile (400 mL) and water (100 mL) is added a solution of 2-cyclopropylmethyl-[1,3]dithiane-2-carboxylic acid ethyl ester (73.2 mmol, 18.05 g) in acetonitrile (50 mL) over 15 minutes. The reaction is warmed and is stirred at room temperature. After 45 minutes, 500 mL of 1:1 hexane/DCM is added. The layers are separated. The organic layer is washed with saturated Na2SO3 (2×225 mL) and brine (2×225 mL), dried with Na2SO4, filtered, and concentrated under reduced pressure to a residue. The residue is diluted in CCl4 and is filtered. The filtrate is concentrated to give the title compound (7 g, 61%). LC-MS: 157.0 (M+1). The reaction is warmed The layers are separated The organic layer is washed with saturated Na2SO3 (2×225 mL) and brine (2×225 mL) dried with Na2SO4 filtered concentrated under reduced pressure to a residue The residue is diluted in CCl4 is filtered The filtrate is concentrated

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

実験手順: To a 0° C. suspension of NBS (439 mmol, 79 g) in a mixture of acetonitrile (400 mL) and water (100 mL) is added a solution of 2-cyclopropylmethyl-[1,3]dithiane-2-carboxylic acid ethyl ester (73.2 mmol, 18.05 g) in acetonitrile (50 mL) over 15 minutes. The reaction is warmed and is stirred at room temperature. After 45 minutes, 500 mL of 1:1 hexane/DCM is added. The layers are separated. The organic layer is washed with saturated Na2SO3 (2×225 mL) and brine (2×225 mL), dried with Na2SO4, filtered, and concentrated under reduced pressure to a residue. The residue is diluted in CCl4 and is filtered. The filtrate is concentrated to give the title compound (7 g, 61%). LC-MS: 157.0 (M+1). The reaction is warmed The layers are separated The organic layer is washed with saturated Na2SO3 (2×225 mL) and brine (2×225 mL) dried with Na2SO4 filtered concentrated under reduced pressure to a residue The residue is diluted in CCl4 is filtered The filtrate is concentrated

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

実験手順: To a flamed dried flask is added dry toluene (80 mL) and sodium hydride (60%, 33.5 mmol, 1.34 g). The reaction is cooled in a ice bath and a solution of ethyl 1,3 dithiane carboxylate (52 mmol, 10 g) and bromomethyl cyclopropane (62.4 mmol, 8.42 g) in DMF (24 mL) are added dropwise over 10 min. The ice bath is removed and the reaction is stirred for 18 h. Water is added (50 mL) and the organic layer is separated. The organic layer is washed with brine, dried (Na2SO4), and concentrated to a yellow oil (12 g, 92%). LC-MS: 247.0 (M+1). To a flamed dried flask The reaction is cooled in a ice bath The ice bath is removed Water is added (50 mL) the organic layer is separated The organic layer is washed with brine dried (Na2SO4) concentrated to a yellow oil (12 g, 92%)