methyl 2-(2,2-dichloro-3-oxocyclobutyl)acetate

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 reaction mixture of methyl but-3-enoate (1.0 g, 10 mmol) and zinc-copper couple (2.0 g, 15.5 mmol) in DME (5 mL) and ether (30 mL) was added trichloroacetyl chloride (2.98 mL, 26.7 mmol) under N2 at rt. The reaction mixture was stirred at rt for 2.5 days. The reaction mixture was filtrated through diatomaceous earth (Celite®) and washed with DCM. The filtrate was concentrated and purified by 80 g silica gel cartridge which was eluted with a 20 min gradient of 0-60% EtOAc in hexane to yield methyl 2-(2,2-dichloro-3-oxocyclobutyl)acetate (1.0 g). 1H NMR (400 MHz, CDCl3) ppm 3.66-3.70 (3H, m), 3.42-3.55 (1H, m), 3.23-3.39 (1H, m), 3.05 (1H, dd, J=17.82, 8.78 Hz), 2.90 (1H, dd, J=16.94, 6.65 Hz), 2.67 (1H, dd, J=16.94, 8.16 Hz). The reaction mixture was filtrated through diatomaceous earth (Celite®) washed with DCM The filtrate was concentrated purified by 80 g silica gel cartridge which was eluted with a 20 min gradient of 0-60% EtOAc in hexane

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of (2,2-dichloro-3-oxo-cyclobutyl)-acetic acid methyl ester (2.93 g, 13.8 mmol) in AcOH (100 ml), zinc powder (4.51 g, 69.0 mmol) is added. The mixture is stirred at 100° C. for 15 hours. The mixture is filtrated and washed with AcOH. The filtrate is concentrated under reduced pressure, and the residue is dissolved in AcOEt, and washed with saturated aqueous NaHCO3 and brine. The organic layer is dried over MgSO4, and concentrated under reduced pressure to give (3-oxo-cyclobutyl)-acetic acid methyl ester (710 mg, 36%); 1H NMR (400 MHz, chloroform-d) δ ppm 2.64-2.66 (m, 2H), 2.78-2.86 (m, 3H), 3.22-3.32 (m, 2H), 3.70 (s, 3H). The mixture is filtrated washed with AcOH The filtrate is concentrated under reduced pressure the residue is dissolved in AcOEt washed with saturated aqueous NaHCO3 and brine The organic layer is dried over MgSO4 concentrated under reduced pressure

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

実験手順: To a mixture of but-3-enoic acid methyl ester (1.00 g, 10 mmol) and zinc-copper couple (1.97 g) in 1,2-dimethoxyethane (4.89 ml) and diethyl ether (37 ml), trichloroacetyl chloride (2.98 ml, 26.7 mmol) is added at room temperature under nitrogen. The mixture is stirred at room temperature for 3 days. The mixture is filtrated and washed with diethyl ether. The filtrate is concentrated under reduced pressure, and the obtained residue is purified by silica gel column chromatography to give (2,2-dichloro-3-oxo-cyclobutyl)-acetic acid methyl ester (2.93 g, quant.); TLC (hexane/AcOEt, 3:1) Rf 0.35, 1H NMR (400 MHz, chloroform-d) δ ppm 2.68-2.74 (m, 1H), 2.94-3.00 (m, 1H), 3.06-3.13 (m, 1H), 3.33-3.41 (m, 1H), 3.51-3.57 (m, 1H), 3.75 (s, 3H). is added at room temperature under nitrogen The mixture is filtrated washed with diethyl ether The filtrate is concentrated under reduced pressure the obtained residue is purified by silica gel column chromatography

反応条件: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of (2,2-dichloro-3-oxo-cyclobutyl)-acetic acid methyl ester (2.93 g, 13.8 mmol) in AcOH (100 ml), zinc powder (4.51 g, 69.0 mmol) is added. The mixture is stirred at 100° C. for 15 hours. The mixture is filtrated and washed with AcOH. The filtrate is concentrated under reduced pressure, and the residue is dissolved in AcOEt, and washed with saturated aqueous NaHCO3 and brine. The organic layer is dried over MgSO4, and concentrated under reduced pressure to give (3-oxo-cyclobutyl)-acetic acid methyl ester (710 mg, 36%); 1H NMR (400 MHz, chloroform-d) δ ppm 2.64-2.66 (m, 2H), 2.78-2.86 (m, 3H), 3.22-3.32 (m, 2H), 3.70 (s, 3H). The mixture is filtrated washed with AcOH The filtrate is concentrated under reduced pressure the residue is dissolved in AcOEt washed with saturated aqueous NaHCO3 and brine The organic layer is dried over MgSO4 concentrated under reduced pressure

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

実験手順: To a mixture of but-3-enoic acid methyl ester (1.00 g, 10 mmol) and zinc-copper couple (1.97 g) in 1,2-dimethoxyethane (4.89 ml) and diethyl ether (37 ml), trichloroacetyl chloride (2.98 ml, 26.7 mmol) is added at room temperature under nitrogen. The mixture is stirred at room temperature for 3 days. The mixture is filtrated and washed with diethyl ether. The filtrate is concentrated under reduced pressure, and the obtained residue is purified by silica gel column chromatography to give (2,2-dichloro-3-oxo-cyclobutyl)-acetic acid methyl ester (2.93 g, quant.); TLC (hexane/AcOEt, 3:1) Rf 0.35, 1H NMR (400 MHz, chloroform-d) δ ppm 2.68-2.74 (m, 1H), 2.94-3.00 (m, 1H), 3.06-3.13 (m, 1H), 3.33-3.41 (m, 1H), 3.51-3.57 (m, 1H), 3.75 (s, 3H). is added at room temperature under nitrogen The mixture is filtrated washed with diethyl ether The filtrate is concentrated under reduced pressure the obtained residue is purified by silica gel column chromatography

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:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of (2,2-dichloro-3-oxo-cyclobutyl)-acetic acid methyl ester (2.93 g, 13.8 mmol) in AcOH (100 ml), zinc powder (4.51 g, 69.0 mmol) is added. The mixture is stirred at 100° C. for 15 hours. The mixture is filtrated and washed with AcOH. The filtrate is concentrated under reduced pressure, and the residue is dissolved in AcOEt, and washed with saturated aqueous NaHCO3 and brine. The organic layer is dried over MgSO4, and concentrated under reduced pressure to give (3-oxo-cyclobutyl)-acetic acid methyl ester (710 mg, 36%); 1H NMR (400 MHz, chloroform-d) δ ppm 2.64-2.66 (m, 2H), 2.78-2.86 (m, 3H), 3.22-3.32 (m, 2H), 3.70 (s, 3H). The mixture is filtrated washed with AcOH The filtrate is concentrated under reduced pressure the residue is dissolved in AcOEt washed with saturated aqueous NaHCO3 and brine The organic layer is dried over MgSO4 concentrated under reduced pressure