methyl 1-(2-bromoethyl)cyclopentane-1-carboxylate

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

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

Procedure: To a solution of 1-(2-bromoethyl)cyclopentane carboxylic acid methyl ester (2.0 mmol, 472 mg) in DMF (5 mL) was added sodium thiomethoxide (2.65 mmol, 186 mg). The reaction mixture was stirred for 15 h at room temperature and was poured into water (30 mL). The organic compound was extracted into diethyl ether (2×20 mL). The combined extracts were washed with a saturated solution of sodium chloride (50 mL) and dried over anhydrous magnesium sulfate. After filtration of the drying agent, the solution was concentrated under vacuum and the resulting residue was purified by silica gel column chromatography to afford 334 mg (82%) of a colorless oil. HR MS C10H18O2S): Obs mass, 202.1024. Calcd mass, 202.1028 (M+). The organic compound was extracted into diethyl ether (2×20 mL) The combined extracts were washed with a saturated solution of sodium chloride (50 mL) dried over anhydrous magnesium sulfate After filtration of the drying agent the solution was concentrated under vacuum the resulting residue was purified by silica gel column chromatography

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

Procedure: To a solution of diisopropylamine (150 mmol, 21 mL) in THF (100 mL) was added dropwise a solution of n-butyl lithium (145 mmol, 58 mL 2.5M) in hexanes at −10° C. while maintaining the temperature below 0° C. After addition, the solution was stirred for 30 min at 0° C. To this, a solution of cyclopentane carboxylic acid methyl ester (100 mmol, 13.1 g) in THF (20 mL) was added dropwise at −70° C. maintaining the internal temperature between −60 to −70° C. After addition, the reaction mixture was stirred for 1 h at −50 to −60° C. Then, a solution of 1,2-dibromoethane (90 mmol, 16.91 g) in THF (20 mL) was added dropwise and the light brown suspension was stirred for 1 h at −60 to −70° C. Then, it was allowed to warm to room temperature and was stirred overnight. The reaction mixture was poured into a saturated solution of ammonium chloride (200 mL) and the organic compound was extracted into ether (2×100 mL). The combined extracts were washed with a saturated solution of sodium chloride (150 mL) and dried over anhydrous magnesium sulfate. After filtration of the drying agent, the solution was concentrated under vacuum and the resulting residue was distilled at 95-105° C./2.5 mm Hg to obtain 11.5 g (49%) of a colorless oil. while maintaining the temperature below 0° C After addition maintaining the internal temperature between −60 to −70° C After addition the reaction mixture was stirred for 1 h at −50 to −60° C the light brown suspension was stirred for 1 h at −60 to −70° C to warm to room temperature was stirred overnight the organic compound was extracted into ether (2×100 mL) The combined extracts were washed with a saturated solution of sodium chloride (150 mL) dried over anhydrous magnesium sulfate After filtration of the drying agent the solution was concentrated under vacuum the resulting residue was distilled at 95-105° C./2.5 mm Hg

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

Procedure: To a solution of 1-(2-bromoethyl)cyclopentane carboxylic acid methyl ester (2.0 mmol, 472 mg) in DMF (5 mL) was added sodium thiomethoxide (2.65 mmol, 186 mg). The reaction mixture was stirred for 15 h at room temperature and was poured into water (30 mL). The organic compound was extracted into diethyl ether (2×20 mL). The combined extracts were washed with a saturated solution of sodium chloride (50 mL) and dried over anhydrous magnesium sulfate. After filtration of the drying agent, the solution was concentrated under vacuum and the resulting residue was purified by silica gel column chromatography to afford 334 mg (82%) of a colorless oil. HR MS C10H18O2S): Obs mass, 202.1024. Calcd mass, 202.1028 (M+). The organic compound was extracted into diethyl ether (2×20 mL) The combined extracts were washed with a saturated solution of sodium chloride (50 mL) dried over anhydrous magnesium sulfate After filtration of the drying agent the solution was concentrated under vacuum the resulting residue was purified by silica gel column chromatography

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

Procedure: To a solution of diisopropylamine (150 mmol, 21 mL) in THF (100 mL) was added dropwise a solution of n-butyl lithium (145 mmol, 58 mL 2.5M) in hexanes at −10° C. while maintaining the temperature below 0° C. After addition, the solution was stirred for 30 min at 0° C. To this, a solution of cyclopentane carboxylic acid methyl ester (100 mmol, 13.1 g) in THF (20 mL) was added dropwise at −70° C. maintaining the internal temperature between −60 to −70° C. After addition, the reaction mixture was stirred for 1 h at −50 to −60° C. Then, a solution of 1,2-dibromoethane (90 mmol, 16.91 g) in THF (20 mL) was added dropwise and the light brown suspension was stirred for 1 h at −60 to −70° C. Then, it was allowed to warm to room temperature and was stirred overnight. The reaction mixture was poured into a saturated solution of ammonium chloride (200 mL) and the organic compound was extracted into ether (2×100 mL). The combined extracts were washed with a saturated solution of sodium chloride (150 mL) and dried over anhydrous magnesium sulfate. After filtration of the drying agent, the solution was concentrated under vacuum and the resulting residue was distilled at 95-105° C./2.5 mm Hg to obtain 11.5 g (49%) of a colorless oil. while maintaining the temperature below 0° C After addition maintaining the internal temperature between −60 to −70° C After addition the reaction mixture was stirred for 1 h at −50 to −60° C the light brown suspension was stirred for 1 h at −60 to −70° C to warm to room temperature was stirred overnight the organic compound was extracted into ether (2×100 mL) The combined extracts were washed with a saturated solution of sodium chloride (150 mL) dried over anhydrous magnesium sulfate After filtration of the drying agent the solution was concentrated under vacuum the resulting residue was distilled at 95-105° C./2.5 mm Hg

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

Procedure: To a solution of diisopropylamine (150 mmol, 21 mL) in THF (100 mL) was added dropwise a solution of n-butyl lithium (145 mmol, 58 mL 2.5M) in hexanes at −10° C. while maintaining the temperature below 0° C. After addition, the solution was stirred for 30 min at 0° C. To this, a solution of cyclopentane carboxylic acid methyl ester (100 mmol, 13.1 g) in THF (20 mL) was added dropwise at −70° C. maintaining the internal temperature between −60 to −70° C. After addition, the reaction mixture was stirred for 1 h at −50 to −60° C. Then, a solution of 1,2-dibromoethane (90 mmol, 16.91 g) in THF (20 mL) was added dropwise and the light brown suspension was stirred for 1 h at −60 to −70° C. Then, it was allowed to warm to room temperature and was stirred overnight. The reaction mixture was poured into a saturated solution of ammonium chloride (200 mL) and the organic compound was extracted into ether (2×100 mL). The combined extracts were washed with a saturated solution of sodium chloride (150 mL) and dried over anhydrous magnesium sulfate. After filtration of the drying agent, the solution was concentrated under vacuum and the resulting residue was distilled at 95-105° C./2.5 mm Hg to obtain 11.5 g (49%) of a colorless oil. while maintaining the temperature below 0° C After addition maintaining the internal temperature between −60 to −70° C After addition the reaction mixture was stirred for 1 h at −50 to −60° C the light brown suspension was stirred for 1 h at −60 to −70° C to warm to room temperature was stirred overnight the organic compound was extracted into ether (2×100 mL) The combined extracts were washed with a saturated solution of sodium chloride (150 mL) dried over anhydrous magnesium sulfate After filtration of the drying agent the solution was concentrated under vacuum the resulting residue was distilled at 95-105° C./2.5 mm Hg

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

Procedure: A solution of 1-[2-bromoethyl]cyclopentanecarboxylic acid methyl ester (49.6 g, 211 mmol) and sodium azide (54 g, 831 mmol) in DMF (200 mL) was stirred at 50° C. for 5 h under nitrogen atmosphere. Then, the solids were filtered and the filtrate was concentrated to near dryness. The residue was diluted with ethyl acetate (500 mL) and the undissolved solids were collected by filtration and the filtrate was concentrated to give the crude ethyl 1-(2-azidoethyl) cyclopentanecarboxylate which was purified by chromatography over 250 g of silica gel, eluting with 5% ethyl acetate in hexane to give 36.2 g (87% yield) of 1-[2-azidoethyl]cyclopentanecarboxylic acid methyl ester as a light brown oil. EI(+)-HRMS m/e calcd. for C9H15N3O2 (M−H)+ 196.1086, obsd. 196.1342. Then, the solids were filtered the filtrate was concentrated The residue was diluted with ethyl acetate (500 mL) the undissolved solids were collected by filtration the filtrate was concentrated to give the crude ethyl 1-(2-azidoethyl) cyclopentanecarboxylate which was purified by chromatography over 250 g of silica gel eluting with 5% ethyl acetate in hexane

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

Procedure: To a solution of diisopropylamine (56 mL, 396 mmol) in TI-IF (85 mL) was added dropwise a solution of n-butyl lithium (240 mL, 393 mmol, 1.6M) in hexanes at −10° C. while maintaining the temperature below 0° C. After addition, the solution was stirred for 30 min at 0° C. To this, a solution of cyclopentanecarboxylic acid methyl ester (37.4 g, 263 mmol) in THF (50 mL) was added dropwise at −70° C. maintaining the internal temperature between −60 to −70° C. After addition, the reaction mixture was stirred for 1 h at −50 to −60° C. Then, a solution of 1,2-dibromoethane (47 mL, 545 mmol) in THF (50 mL) was added dropwise and the light brown suspension was stirred for 1 h at −70 to −60° C. Then, it was allowed to warm to room temperature and stirred overnight. The reaction mixture was poured into a saturated aqueous solution of ammonium chloride (200 mL) and the organic compound was extracted into ether (2×100 mL). The combined extracts were washed with a saturated solution of sodium chloride (150 mL) and dried over anhydrous magnesium sulfate. After filtration of the drying agent, the solution was concentrated under vacuum and the resulting residue was distilled at 95-105° C./2.5 mm Hg to obtain 49.6 g (80% yield) of 1-[2-bromoethyl]cyclopentanecarboxylic acid methyl ester as a colorless oil. while maintaining the temperature below 0° C After addition maintaining the internal temperature between −60 to −70° C After addition the reaction mixture was stirred for 1 h at −50 to −60° C the light brown suspension was stirred for 1 h at −70 to −60° C to warm to room temperature stirred overnight the organic compound was extracted into ether (2×100 mL) The combined extracts were washed with a saturated solution of sodium chloride (150 mL) dried over anhydrous magnesium sulfate After filtration of the drying agent the solution was concentrated under vacuum the resulting residue was distilled at 95-105° C./2.5 mm Hg

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 1-[2-bromoethyl]cyclopentanecarboxylic acid methyl ester (49.6 g, 211 mmol) and sodium azide (54 g, 831 mmol) in DMF (200 mL) was stirred at 50° C. for 5 h under nitrogen atmosphere. Then, the solids were filtered and the filtrate was concentrated to near dryness. The residue was diluted with ethyl acetate (500 mL) and the undissolved solids were collected by filtration and the filtrate was concentrated to give the crude ethyl 1-(2-azidoethyl) cyclopentanecarboxylate which was purified by chromatography over 250 g of silica gel, eluting with 5% ethyl acetate in hexane to give 36.2 g (87% yield) of 1-[2-azidoethyl]cyclopentanecarboxylic acid methyl ester as a light brown oil. EI(+)-HRMS m/e calcd. for C9H15N3O2 (M−H)+ 196.1086, obsd. 196.1342. Then, the solids were filtered the filtrate was concentrated The residue was diluted with ethyl acetate (500 mL) the undissolved solids were collected by filtration the filtrate was concentrated to give the crude ethyl 1-(2-azidoethyl) cyclopentanecarboxylate which was purified by chromatography over 250 g of silica gel eluting with 5% ethyl acetate in hexane

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

Procedure: To a solution of diisopropylamine (56 mL, 396 mmol) in TI-IF (85 mL) was added dropwise a solution of n-butyl lithium (240 mL, 393 mmol, 1.6M) in hexanes at −10° C. while maintaining the temperature below 0° C. After addition, the solution was stirred for 30 min at 0° C. To this, a solution of cyclopentanecarboxylic acid methyl ester (37.4 g, 263 mmol) in THF (50 mL) was added dropwise at −70° C. maintaining the internal temperature between −60 to −70° C. After addition, the reaction mixture was stirred for 1 h at −50 to −60° C. Then, a solution of 1,2-dibromoethane (47 mL, 545 mmol) in THF (50 mL) was added dropwise and the light brown suspension was stirred for 1 h at −70 to −60° C. Then, it was allowed to warm to room temperature and stirred overnight. The reaction mixture was poured into a saturated aqueous solution of ammonium chloride (200 mL) and the organic compound was extracted into ether (2×100 mL). The combined extracts were washed with a saturated solution of sodium chloride (150 mL) and dried over anhydrous magnesium sulfate. After filtration of the drying agent, the solution was concentrated under vacuum and the resulting residue was distilled at 95-105° C./2.5 mm Hg to obtain 49.6 g (80% yield) of 1-[2-bromoethyl]cyclopentanecarboxylic acid methyl ester as a colorless oil. while maintaining the temperature below 0° C After addition maintaining the internal temperature between −60 to −70° C After addition the reaction mixture was stirred for 1 h at −50 to −60° C the light brown suspension was stirred for 1 h at −70 to −60° C to warm to room temperature stirred overnight the organic compound was extracted into ether (2×100 mL) The combined extracts were washed with a saturated solution of sodium chloride (150 mL) dried over anhydrous magnesium sulfate After filtration of the drying agent the solution was concentrated under vacuum the resulting residue was distilled at 95-105° C./2.5 mm Hg

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

Procedure: To a solution of 1-(2-bromoethyl)cyclopentane carboxylic acid methyl ester (2.0 mmol, 472 mg) in DMF (5 mL) was added sodium thiomethoxide (2.65 mmol, 186 mg). The reaction mixture was stirred for 15 h at room temperature and was poured into water (30 mL). The organic compound was extracted into diethyl ether (2×20 mL). The combined extracts were washed with a saturated solution of sodium chloride (50 mL) and dried over anhydrous magnesium sulfate. After filtration of the drying agent, the solution was concentrated under vacuum and the resulting residue was purified by silica gel column chromatography to afford 334 mg (82%) of a colorless oil. HR MS C10H18O2S): Obs mass, 202.1024. Calcd mass, 202.1028 (M+). The organic compound was extracted into diethyl ether (2×20 mL) The combined extracts were washed with a saturated solution of sodium chloride (50 mL) dried over anhydrous magnesium sulfate After filtration of the drying agent the solution was concentrated under vacuum the resulting residue was purified by silica gel column chromatography