methyl 4-iodobutanoate

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

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

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

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

Procedure: A mixture of 64.0 g. (0.28 mole) of methyl γ-iodobutyrate, 28.0 g. (0.28 mole) of triethylamine, 28.7 g. (0.28 mole) of thiomorpholine (J. Am. Chem. Soc. 76, 1187 (1954)) and 1 liter of benzene was stirred and heated at 60°-70°C. for 18 hours. After cooling the reaction mixture, the precipitated amine hydroiodide was removed by suction filtration. The benzene solution was evaporated to give a orange-red residue which was vacuum distilled (b.p. 84°-85°C. at 0.1 mm) to give 28.38 g. (50%) of the product as a colorless liquid. A mixture of 64.0 g heated at 60°-70°C. for 18 hours After cooling the reaction mixture the precipitated amine hydroiodide was removed by suction filtration The benzene solution was evaporated to give a orange-red residue which distilled (b.p. 84°-85°C. at 0.1 mm) to give 28.38 g

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

Procedure: A mixture of 64.0 g. (0.28 mole) of methyl γ-iodobutyrate, 28.0 g. (0.28 mole) of triethylamine, 28.7 g. (0.28 mole) of thiomorpholine (J. Am. Chem. Soc. 76, 1187 (1954)) and 1 liter of benzene was stirred and heated at 60°-70°C. for 18 hours. After cooling the reaction mixture, the precipitated amine hydroiodide was removed by suction filtration. The benzene solution was evaporated to give a orange-red residue which was vacuum distilled (b.p. 84°-85°C. at 0.1 mm) to give 28.38 g. (50%) of the product as a colorless liquid. A mixture of 64.0 g heated at 60°-70°C. for 18 hours After cooling the reaction mixture the precipitated amine hydroiodide was removed by suction filtration The benzene solution was evaporated to give a orange-red residue which distilled (b.p. 84°-85°C. at 0.1 mm) to give 28.38 g

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

Procedure: 30.0 g. (0.13 mole) of Methyl γ-iodobutyrate (Blicke et al., J. Am. Chem. Soc. 63, 2488 (1941)) was combined with 36 g. of pyrrolidine in 300 ml. of benzene, heated at 60°C. for 0.5 hour and stirred at room temperature for 16 hours. A dark orange layer formed. The benzene solution was decanted, concentrated and distilled (b.p. 100°C. at 15 mm Hg) to give 10 g. of colorless liquid. The infrared and nuclear magnetic resonance spectra indicated the product to be methyl γ-pyrrolidino-butyrate. This material was dissolved in 100 ml. of 18% hydrochloric acid and heated at reflux for 28 hours. The solution was concentrated under reduced pressure to give a semi-solid which was triturated with acetone and filtered. Recrystallization from acetic acid/acetone gave 8.3 g. (33%) of the desired acid hydrochloride as colorless crystals, m.p. 126°-127°C. The infrared and nuclear magnetic resonance spectra were consistent with the proposed structure. A dark orange layer formed The benzene solution was decanted concentrated distilled (b.p. 100°C. at 15 mm Hg) to give 10 g This material was dissolved in 100 ml at reflux for 28 hours The solution was concentrated under reduced pressure to give a semi-solid which was triturated with acetone filtered Recrystallization from acetic acid/acetone gave 8.3 g

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

Procedure: 30.0 g. (0.13 mole) of Methyl γ-iodobutyrate (Blicke et al., J. Am. Chem. Soc. 63, 2488 (1941)) was combined with 36 g. of pyrrolidine in 300 ml. of benzene, heated at 60°C. for 0.5 hour and stirred at room temperature for 16 hours. A dark orange layer formed. The benzene solution was decanted, concentrated and distilled (b.p. 100°C. at 15 mm Hg) to give 10 g. of colorless liquid. The infrared and nuclear magnetic resonance spectra indicated the product to be methyl γ-pyrrolidino-butyrate. This material was dissolved in 100 ml. of 18% hydrochloric acid and heated at reflux for 28 hours. The solution was concentrated under reduced pressure to give a semi-solid which was triturated with acetone and filtered. Recrystallization from acetic acid/acetone gave 8.3 g. (33%) of the desired acid hydrochloride as colorless crystals, m.p. 126°-127°C. The infrared and nuclear magnetic resonance spectra were consistent with the proposed structure. A dark orange layer formed The benzene solution was decanted concentrated distilled (b.p. 100°C. at 15 mm Hg) to give 10 g This material was dissolved in 100 ml at reflux for 28 hours The solution was concentrated under reduced pressure to give a semi-solid which was triturated with acetone filtered Recrystallization from acetic acid/acetone gave 8.3 g

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

Procedure: A mixture of 64.0 g. (0.28 mole) of methyl γ-iodobutyrate, 28.0 g. (0.28 mole) of triethylamine, 28.7 g. (0.28 mole) of thiomorpholine (J. Am. Chem. Soc. 76, 1187 (1954)) and 1 liter of benzene was stirred and heated at 60°-70°C. for 18 hours. After cooling the reaction mixture, the precipitated amine hydroiodide was removed by suction filtration. The benzene solution was evaporated to give a orange-red residue which was vacuum distilled (b.p. 84°-85°C. at 0.1 mm) to give 28.38 g. (50%) of the product as a colorless liquid. A mixture of 64.0 g heated at 60°-70°C. for 18 hours After cooling the reaction mixture the precipitated amine hydroiodide was removed by suction filtration The benzene solution was evaporated to give a orange-red residue which distilled (b.p. 84°-85°C. at 0.1 mm) to give 28.38 g

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

Procedure: 30.0 g. (0.13 mole) of Methyl γ-iodobutyrate (Blicke et al., J. Am. Chem. Soc. 63, 2488 (1941)) was combined with 36 g. of pyrrolidine in 300 ml. of benzene, heated at 60°C. for 0.5 hour and stirred at room temperature for 16 hours. A dark orange layer formed. The benzene solution was decanted, concentrated and distilled (b.p. 100°C. at 15 mm Hg) to give 10 g. of colorless liquid. The infrared and nuclear magnetic resonance spectra indicated the product to be methyl γ-pyrrolidino-butyrate. This material was dissolved in 100 ml. of 18% hydrochloric acid and heated at reflux for 28 hours. The solution was concentrated under reduced pressure to give a semi-solid which was triturated with acetone and filtered. Recrystallization from acetic acid/acetone gave 8.3 g. (33%) of the desired acid hydrochloride as colorless crystals, m.p. 126°-127°C. The infrared and nuclear magnetic resonance spectra were consistent with the proposed structure. A dark orange layer formed The benzene solution was decanted concentrated distilled (b.p. 100°C. at 15 mm Hg) to give 10 g This material was dissolved in 100 ml at reflux for 28 hours The solution was concentrated under reduced pressure to give a semi-solid which was triturated with acetone filtered Recrystallization from acetic acid/acetone gave 8.3 g

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

Procedure: 30.0 g. (0.13 mole) of Methyl γ-iodobutyrate (F.F. Blicke, W. B. Wright and M. F. Zienty, J. Amer. Chem. Soc. 63, 2488 (1941) was combined with 36 g. of pyrrolidine (Aldrich) in 300 ml. of benzene, heated at 60° for 0.5 hours and stirred at room temperature for 16 hours. A dark orange layer formed. The benzene solution was decanted, concentrated and distilled (b.p. 100° at 15 mm Hg) to give 10 g. of colorless liquid. The infrared and nmr spectra indicated the product to be methyl γ-pyrrolidinobutyrate. This material was dissolved in 100 ml. of 18% hydrochloric acid and heated at reflux for 28 hours. The solution was concentrated under reduced pressure to give a semi-solid which was triturated with acetone and filtered. Recrystallization from acetic acid/acetone gave 8.3 g. (33%) of the desired acid hydrochloride as colorless crystals, m.p. 126°-127° . The infrared and nmr spectra are consistent with the proposed structure. A dark orange layer formed The benzene solution was decanted concentrated distilled (b.p. 100° at 15 mm Hg) to give 10 g This material was dissolved in 100 ml at reflux for 28 hours The solution was concentrated under reduced pressure to give a semi-solid which was triturated with acetone filtered Recrystallization from acetic acid/acetone gave 8.3 g

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

Procedure: 30.0 g. (0.13 mole) of Methyl γ-iodobutyrate (F.F. Blicke, W.B. Wright and M.F. Zienty, J. Amer. Chem. Soc. 63, 2488 (1941) was combined with 36 g. of pyrrolidine (Aldrich) in 300 ml. of benzene, heated at 60° for 0.5 hour and stirred at room temperature for 16 hours. A dark orange layer formed. The benzene solution was decanted, concentrated and distilled (b.p. 100° at 15 mm Hg) to give 10 g. of colorless liquid. The infrared and nmr spectra indicated that product to be methyl Γ-pyrrolidinobutyrate. This material was dissolved in 100 ml. of 18% hydrochloric acid and heated at reflux for 28 hours. The solution was concentrated under reduced pressure to give a semi-solid which was triturated with acetone and filtered. Recrystallization from acetic acid/acetone gave 8.3 g. (33%) of the desired acid hydrochloride as colorless crystals, m.p. 126°-127°. The infrared and nmr spectra are consistent with the proposed structure. A dark orange layer formed The benzene solution was decanted concentrated distilled (b.p. 100° at 15 mm Hg) to give 10 g This material was dissolved in 100 ml at reflux for 28 hours The solution was concentrated under reduced pressure to give a semi-solid which was triturated with acetone filtered Recrystallization from acetic acid/acetone gave 8.3 g

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

Procedure: Heat a suspension of methyl 4-bromo-2-isopropoxycarbonylaminobenzoate (19.2 g, 60.7 mmol), methyl 4-iodobutyrate (16.4 mL, 121 mmol) and cesium carbonate (39.6 g, 121 mmol) in N,N-dimethylformamide (240 mL) under nitrogen at 80° C. for 24 h. Cool the mixture to room temperature and pour into a saturated ammonium chloride solution (500 mL) and extract with ethyl acetate (3×200 mL). Combine the organic extracts and wash with water (2×400 mL), brine (100 mL), then dry the solution over sodium sulfate, filter and remove the solvent under reduced pressure. Purify the residue using chromatography on silica gel, eluting with hexanes/ethyl acetate (60:40), to provide the title compound as an orange oil (15.9 g, 63%): APCI MS 416 (M+H Heat extract with ethyl acetate (3×200 mL) Combine the organic extracts and wash with water (2×400 mL), brine (100 mL) dry the solution over sodium sulfate filter remove the solvent under reduced pressure Purify the residue eluting with hexanes/ethyl acetate (60:40)