ethyl 1-benzylcyclobutane-1-carboxylate

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

Procedure: A mixture of ethyl 1-phenylmethylcyclobutanecarboxylate (4.16 g, 19.1 mmol), sodium hydroxide (1.2 g, 30 mmol) in ethanol (95%, 20 ml) and water (5 ml) was stirred at room temperature for 60 hours. The reaction mixture was poured into cold water and extracted with diethyl ether. The aqueous phase was separated, acidified with HCl (2N, 35 ml) and extracted with diethyl ether. The latter extract was washed with water, dried, filtered and evaporated to afford the desired product as a pale yellow oil: NMR (CDCl3) δ=1.7~2.6 (6H, m), 3.10 (2H, s), 7.22 (5H, s). extracted with diethyl ether The aqueous phase was separated extracted with diethyl ether The latter extract was washed with water dried filtered evaporated

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

Procedure: A mixture of ethyl 1-phenylmethylcyclobutanecarboxylate (4.16 g, 19.1 mmol), sodium hydroxide (1.2 g, 30 mmol) in ethanol (95%, 20 ml and water (5 ml) was stirred at room temperature for 60 hours. The reaction mixture was poured into cold water and extracted with diethyl ether. The aqueous Phase was separated, acidified with HCl (2N, 35 ml) and extracted with diethyl ether. The latter extract was washed with water, dried, filtered and evaporated to afford the desired product as a pale yellow oil: NMR (CDCl3) δ=1.7~2.6 (6H, m), 3.10 (2H, s), 7.22 (5H, s). extracted with diethyl ether The aqueous Phase was separated extracted with diethyl ether The latter extract was washed with water dried filtered evaporated

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

Procedure: A mixture of ethyl 1-phenylmethylcyclobutanecarboxylate (4.16 g, 19.1 mmol), sodium hydroxide (1.2 g, 30 mmol) in ethanol (95%, 20 ml and water (5 ml) was stirred at room temperature for 60 hours. The reaction mixture was poured into cold water and extracted with diethyl ether. The aqueous Phase was separated, acidified with HCl (2N, 35 ml) and extracted with diethyl ether. The latter extract was washed with water, dried, filtered and evaporated to afford the desired product as a pale yellow oil: NMR (CDCl3) δ=1.7~2.6 (6H, m), 3.10 (2H, s), 7.22 (5H, s). extracted with diethyl ether The aqueous Phase was separated extracted with diethyl ether The latter extract was washed with water dried filtered evaporated

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

Procedure: A mixture of ethyl 1-phenylmethylcyclobutanecarboxylate (4.16 g, 19.1 mmol), sodium hydroxide (1.2 g, 30 mmol) in ethanol (95%, 20 ml) and water (5 ml) was stirred at room temperature for 60 hours. The reaction mixture was poured into cold water and extracted with diethyl ether. The aqueous phase was separated, acidified with HCl (2N, 35 ml) and extracted with diethyl ether. The latter extract was washed with water, dried, filtered and evaporated to afford the desired product as a pale yellow oil: NMR (CDCl3) δ=1.7~2.6 (6H, m), 3.10 (2H, s), 7.22 (5H, s). extracted with diethyl ether The aqueous phase was separated extracted with diethyl ether The latter extract was washed with water dried filtered evaporated

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

Procedure: To a −78° C. solution of 2.8 mL (20.0 mmol) of diisopropylamine in 40 mL of dry tetrahydrofuran was added 13.75 mL (22 mmol) of 1.6 M n-butyllithium in hexanes. The reaction was let warm to 0° C. and then cooled to −78° C. A solution of 2.7 mL (20 mmol) of ethyl cyclobutanecarboxylate in 10 mL of tetrahydrofuran was added dropwise and the reaction let warm to 0° C. The reaction was stirred for 15 min before being cooled to −78° C. To the solution was added 3.1 mL (26 mmol) of benzyl bromide dropwise and the reaction stirred for 15 min before being let warm to room temperature and stirred overnight. The reaction was quenched with water and extracted with ethyl acetate. The organic phase was washed with saturated ammonium chloride, washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure to afford 5.24 g of crude ethyl 1-benzylcyclobutanecarboxylate. The crude product was dissolved in 100 mL of tetrahydrofuran and cooled to 0° C. To this solution was added dropwise 14.1 mL (14.1 mmol) of 1M lithium aluminum hydride in tetrahydrofuran. The reaction was stirred for 1 h before being carefully quenched with brine. The mixture was filtered through a celite plug and the filter cake washed with ethyl acetate. The filtrate was washed with brine, dried over magnesium sulfate, and concentrated under reduced pressure to afford 1.6 g (45%) of ethyl (1-benzylcyclobutyl)methanol. 1H NMR (300 MHz, DMSO-d6) δ 7.18-7.34 (m, 5H), 4.63 (t, J=5 Hz, 1H), 3.24-3.25 (d, J=5H, 2H), 2.71 (s, 2H), 1.66-1.79 (m, 6H). cooled to −78° C the reaction let warm to 0° C before being cooled to −78° C the reaction stirred for 15 min before being let warm to room temperature stirred overnight The reaction was quenched with water extracted with ethyl acetate The organic phase was washed with saturated ammonium chloride washed with brine dried over magnesium sulfate concentrated under reduced pressure

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

Procedure: A mixture of ethyl 1-phenylmethylcyclobutanecarboxylate (4.16 g, 19.1 mmol), sodium hydroxide (1.2 g, 30 mmol) in ethanol (95%, 20 ml and water (5 ml) was stirred at room temperature for 60 hours. The reaction mixture was poured into cold water and extracted with diethyl ether. The aqueous Phase was separated, acidified with HCl (2N, 35 ml) and extracted with diethyl ether. The latter extract was washed with water, dried, filtered and evaporated to afford the desired product as a pale yellow oil: NMR (CDCl3) δ=1.7~2.6 (6H, m), 3.10 (2H, s), 7.22 (5H, s). extracted with diethyl ether The aqueous Phase was separated extracted with diethyl ether The latter extract was washed with water dried filtered evaporated

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

Procedure: A mixture of ethyl 1-phenylmethylcyclobutanecarboxylate (4.16 g, 19.1 mmol), sodium hydroxide (1.2 g, 30 mmol) in ethanol (95%, 20 ml) and water (5 ml) was stirred at room temperature for 60 hours. The reaction mixture was poured into cold water and extracted with diethyl ether. The aqueous phase was separated, acidified with HCl (2N, 35 ml) and extracted with diethyl ether. The latter extract was washed with water, dried, filtered and evaporated to afford the desired product as a pale yellow oil: NMR (CDCl3) δ=1.7~2.6 (6H, m), 3.10 (2H, s), 7.22 (5H, s). extracted with diethyl ether The aqueous phase was separated extracted with diethyl ether The latter extract was washed with water dried filtered evaporated