ethyl 3-oxocyclopentane-1-carboxylate

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: A solution of cyclopentanone-3-carboxylic acid (5.00 g, 39 mmol), caesium carbonate (12.82 g, 39 mmol) and ethyl iodide (9.12 g, 4.75 ml, 58.5 mmol) in DMF (50 ml) was stirred at RT for 18 h. The mixture was then concentrated i. vac., the residue was taken up in toluene, the mixture was concentrated again and 2 N hydrochloric acid and EtOAc were then added. The aq. phase was extracted with EtOAc (3×30 ml) and the combined organic phases were washed with aq. sodium thiosulfate soln. The organic phase was dried with Na2SO4 and concentrated i. vac. The mixture was then concentrated i the mixture was concentrated again 2 N hydrochloric acid and EtOAc were then added The aq. phase was extracted with EtOAc (3×30 ml) the combined organic phases were washed with aq. sodium thiosulfate soln The organic phase was dried with Na2SO4 concentrated i

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

Procedure: To a 0° C. solution of ethyl-3-oxo-cyclopentane-1-carboxylate (2.0 g) in THF (50 mL) was added NaBH4 (970 mg). The reaction mixture was maintained at 0° C. for 30 min, and then overnight at ambient temperature. The reaction was then treated with H2O and diluted with Et2O. The resulting layers were separated, and the aqueous layer was further extracted with Et2O. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The resulting crude product (a mixture of cis/trans isomers) was used in the next step without further purification. overnight at ambient temperature The resulting layers were separated the aqueous layer was further extracted with Et2O The combined organic layers were washed with brine dried over Na2SO4 filtered concentrated The resulting crude product (a mixture of cis/trans isomers) was used in the next step without further purification

Conditions: temp:0.00; pressure:0.00; stir:

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

Procedure: A solution of cyclopentanone-3-carboxylic acid (5.00 g, 39 mmol), caesium carbonate (12.82 g, 39 mmol) and ethyl iodide (9.12 g, 4.75 ml, 58.5 mmol) in DMF (50 ml) was stirred at RT for 18 h. The mixture was then concentrated i. vac., the residue was taken up in toluene, the mixture was concentrated again and 2 N hydrochloric acid and EtOAc were then added. The aq. phase was extracted with EtOAc (3×30 ml) and the combined organic phases were washed with aq. sodium thiosulfate soln. The organic phase was dried with Na2SO4 and concentrated i. vac. The mixture was then concentrated i the mixture was concentrated again 2 N hydrochloric acid and EtOAc were then added The aq. phase was extracted with EtOAc (3×30 ml) the combined organic phases were washed with aq. sodium thiosulfate soln The organic phase was dried with Na2SO4 concentrated i

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

Procedure: To a 0° C. solution of ethyl-3-oxo-cyclopentane-1-carboxylate (2.0 g) in THF (50 mL) was added NaBH4 (970 mg). The reaction mixture was maintained at 0° C. for 30 min, and then overnight at ambient temperature. The reaction was then treated with H2O and diluted with Et2O. The resulting layers were separated, and the aqueous layer was further extracted with Et2O. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The resulting crude product (a mixture of cis/trans isomers) was used in the next step without further purification. overnight at ambient temperature The resulting layers were separated the aqueous layer was further extracted with Et2O The combined organic layers were washed with brine dried over Na2SO4 filtered concentrated The resulting crude product (a mixture of cis/trans isomers) was used in the next step without further purification

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

Procedure: To a 0° C. solution of ethyl-3-oxo-cyclopentane-1-carboxylate (2.0 g) in THF (50 mL) was added NaBH4 (970 mg). The reaction mixture was maintained at 0° C. for 30 min, and then overnight at ambient temperature. The reaction was then treated with H2O and diluted with Et2O. The resulting layers were separated, and the aqueous layer was further extracted with Et2O. The combined organic layers were washed with brine, dried over Na2SO4, filtered and concentrated. The resulting crude product (a mixture of cis/trans isomers) was used in the next step without further purification. overnight at ambient temperature The resulting layers were separated the aqueous layer was further extracted with Et2O The combined organic layers were washed with brine dried over Na2SO4 filtered concentrated The resulting crude product (a mixture of cis/trans isomers) was used in the next step without further purification

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

Procedure: To 250 ml of 80% acetic acid in water, were added 4-phenylmethoxyphenylhydrazine hydrochloride (30 g, 0.12 mole) and 3-oxocyclopentane carboxylic acid ethyl ester (20 g, 0.13 mole). After stirring at ambient temperature for one hour and then at 100° C. for four hours, the mixture was cooled and poured into one liter of water. After stirring for five minutes, the mixture was extracted with ethyl acetate (3×). The organic layer was washed successively with water (2×) and saturated sodium chloride solution, and thereafter dried over anhydrous MgSO4. After filtering, the solution was concentrated to a dark oil (~48 g), which was eluted on a silica gel column with 5% ethyl acetate/dichloromethane via HPLC. The desired fractions were combined and concentrated to give the product as a thick brown oil (24.1 g). at 100° C. for four hours the mixture was cooled After stirring for five minutes the mixture was extracted with ethyl acetate (3×) The organic layer was washed successively with water (2×) and saturated sodium chloride solution dried over anhydrous MgSO4 After filtering the solution was concentrated to a dark oil (~48 g), which was eluted on a silica gel column with 5% ethyl acetate/dichloromethane via HPLC concentrated

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

Procedure: To 250 ml of 80% acetic acid in water, were added 4-phenylmethoxyphenylhydrazine hydrochloride (30 g, 0.12 mole) and 3-oxocyclopentane carboxylic acid ethyl ester (20 g, 0.13 mole). After stirring at ambient temperature for one hour and then at 100° C. for four hours, the mixture was cooled and poured into one liter of water. After stirring for five minutes, the mixture was extracted with ethyl acetate (3×). The organic layer was washed successively with water (2×) and saturated sodium chloride solution, and thereafter dried over anhydrous MgSO4. After filtering, the solution was concentrated to a dark oil (~48 g), which was eluted on a silica gel column with 5% ethyl acetate/dichloromethane via HPLC. The desired fractions were combined and concentrated to give the product as a thick brown oil (24.1 g). at 100° C. for four hours the mixture was cooled After stirring for five minutes the mixture was extracted with ethyl acetate (3×) The organic layer was washed successively with water (2×) and saturated sodium chloride solution dried over anhydrous MgSO4 After filtering the solution was concentrated to a dark oil (~48 g), which was eluted on a silica gel column with 5% ethyl acetate/dichloromethane via HPLC concentrated

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

Procedure: To 250 ml of 80% acetic acid in water, were added 4-phenylmethoxyphenylhydrazine hydrochloride (30 g, 0.12 mole) and 3-oxocyclopentane carboxylic acid ethyl ester (20 g, 0.13 mole). After stirring at ambient temperature for one hour and then at 100° C. for four hours, the mixture was cooled and poured into one liter of water. After stirring for five minutes, the mixture was extracted with ethyl acetate (3×). The organic layer was washed successively with water (2×) and saturated sodium chloride solution, and thereafter dried over anhydrous MgSO4. After filtering, the solution was concentrated to a dark oil (~48 g), which was eluted on a silica gel column with 5% ethyl acetate/dichloromethane via HPLC. The desired fractions were combined and concentrated to give the product as a thick brown oil (24.1 g). at 100° C. for four hours the mixture was cooled After stirring for five minutes the mixture was extracted with ethyl acetate (3×) The organic layer was washed successively with water (2×) and saturated sodium chloride solution dried over anhydrous MgSO4 After filtering the solution was concentrated to a dark oil (~48 g), which was eluted on a silica gel column with 5% ethyl acetate/dichloromethane via HPLC concentrated

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

Procedure: A solution of THF:toluene (2.11 mL:2.11 mL) and n-BuLi (0.923 ml, 1.48 mmol) was cooled to −10° C. The reaction mixture was purged/filled with argon (3×). n-Butyl magnesium chloride (0.369 ml, 0.739 mmol) was added to the reaction mixture and stirred for 30 minutes. 3,5-Dibromopyridine (0.5 g, 2.111 mmol) was added to the reaction mixture over the course of 30 minutes, keeping bath below −10° C. and stirred for 1 hour. Ethyl 3-oxocyclopentanecarboxylate (0.330 g, 2.111 mmol) was added to the reaction mixture and stirred at −10° C. for ˜5 minutes. The reaction mixture was warmed to room temperature, diluted with saturated ammonium, extracted DCM (3×), and combined organic layers were concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/hexanes) to afford ethyl 3-(5-bromopyridin-3-yl)-3-hydroxycyclopentanecarboxylate. MS ESI calc'd for C13H17BrNO3 [M+H]+ 314 and 316. found 314 and 316. The reaction mixture was purged/filled with argon (3×) below −10° C. stirred for 1 hour stirred at −10° C. for ˜5 minutes extracted DCM (3×) were concentrated under reduced pressure The residue was purified by silica gel chromatography (ethyl acetate/hexanes)

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

Procedure: A solution of THF:toluene (2.11 mL:2.11 mL) and n-BuLi (0.923 ml, 1.48 mmol) was cooled to −10° C. The reaction mixture was purged/filled with argon (3×). n-Butyl magnesium chloride (0.369 ml, 0.739 mmol) was added to the reaction mixture and stirred for 30 minutes. 3,5-Dibromopyridine (0.5 g, 2.111 mmol) was added to the reaction mixture over the course of 30 minutes, keeping bath below −10° C. and stirred for 1 hour. Ethyl 3-oxocyclopentanecarboxylate (0.330 g, 2.111 mmol) was added to the reaction mixture and stirred at −10° C. for ˜5 minutes. The reaction mixture was warmed to room temperature, diluted with saturated ammonium, extracted DCM (3×), and combined organic layers were concentrated under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate/hexanes) to afford ethyl 3-(5-bromopyridin-3-yl)-3-hydroxycyclopentanecarboxylate. MS ESI calc'd for C13H17BrNO3 [M+H]+ 314 and 316. found 314 and 316. The reaction mixture was purged/filled with argon (3×) below −10° C. stirred for 1 hour stirred at −10° C. for ˜5 minutes extracted DCM (3×) were concentrated under reduced pressure The residue was purified by silica gel chromatography (ethyl acetate/hexanes)