1-pyrrolidin-1-ylpent-4-yn-1-one

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

Procedure: 4-Pentynoic acid (500 mg, 5.1 mmol), EDCI (1.56 g, 7.7 mmol) and HOBt (1.411 g, 10.2 mmol) were dissolved in 20 mL of DCM under inert atmosphere. A mixture of pyrrolidine (850 uL, 10.2 mmol) and DIPEA (4.5 mL, 25.5 mmol) in 3 mL DCM was added and the mixture was stirred for 2 h. The mixture was quenched with 25 mL 10% citric acid, stirred for 5 min., the organic layer was collected and the aqueous layer was extracted with 2×20 mL DCM. The combined organic layers were washed with 20 mL 10% citric acid. The DCM layer was washed with 20 mL saturated sodium bicarbonate, 20 mL brine and dried over sodium sulfate. The filtrates were concentrated and the residue was adsorbed on silica gel and chromatographed on silica gel (12 g) using 0→20% EtOAc-DCM to give 620 mg of 1-(pyrrolidin-1-yl)pent-4-yn-1-one. was added The mixture was quenched with 25 mL 10% citric acid stirred for 5 min. the organic layer was collected the aqueous layer was extracted with 2×20 mL DCM The combined organic layers were washed with 20 mL 10% citric acid The DCM layer was washed with 20 mL saturated sodium bicarbonate, 20 mL brine dried over sodium sulfate The filtrates were concentrated chromatographed on silica gel (12 g)

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

Procedure: To a solution of 4-pentynoic acid (981 mg, 10 mmol) in THF (40 mL) and DMF (2 drops) was added dropwise oxalyl chloride (0.96 mL, 11 mmol) over 10 min. The solution was stirred for 3 h at rt, then the flask was cooled in an ice bath and a solution of pyrrolidine (1.65 mL, 20 mmol) and Et3N (1.74 mL, 12.5 mmol) in THF (10 mL) was added dropwise over 17 min. The resulting suspension was stirred overnight, then filtered. The filtrate was partitioned between EtOAc (300 mL) and H2O. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were dried (Na2SO4) and concentrated to dryness, giving the desired product as a brown solid (1.32 g, 87%). MS (APCI(+)) m/e 152.1 (M+H)+. the flask was cooled in an ice bath The resulting suspension was stirred overnight filtered The filtrate was partitioned between EtOAc (300 mL) and H2O The layers were separated the aqueous layer was extracted with EtOAc The combined organic layers were dried (Na2SO4) concentrated to dryness

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

Procedure: To a solution of 4-pentynoic acid (981 mg, 10 mmol) in THF (40 mL) and DMF (2 drops) was added dropwise oxalyl chloride (0.96 mL, 11 mmol) over 10 min. The solution was stirred for 3 h at rt, then the flask was cooled in an ice bath and a solution of pyrrolidine (1.65 mL, 20 mmol) and Et3N (1.74 mL, 12.5 mmol) in THF (10 mL) was added dropwise over 17 min. The resulting suspension was stirred overnight, then filtered. The filtrate was partitioned between EtOAc (300 mL) and H2O. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were dried (Na2SO4) and concentrated to dryness, giving the desired product as a brown solid (1.32 g, 87%). MS (APCI(+)) m/e 152.1 (M+H)+. the flask was cooled in an ice bath The resulting suspension was stirred overnight filtered The filtrate was partitioned between EtOAc (300 mL) and H2O The layers were separated the aqueous layer was extracted with EtOAc The combined organic layers were dried (Na2SO4) concentrated to dryness

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

Procedure: To a solution of 4-pentynoic acid (981 mg, 10 mmol) in THF (40 mL) and DMF (2 drops) was added dropwise oxalyl chloride (0.96 mL, 11 mmol) over 10 min. The solution was stirred for 3 h at rt, then the flask was cooled in an ice bath and a solution of pyrrolidine (1.65 mL, 20 mmol) and Et3N (1.74 mL, 12.5 mmol) in THF (10 mL) was added dropwise over 17 min. The resulting suspension was stirred overnight, then filtered. The filtrate was partitioned between EtOAc (300 mL) and H2O. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic layers were dried (Na2SO4) and concentrated to dryness, giving the desired product as a brown solid (1.32 g, 87%). MS (APCI(+)) m/e 152.1 (M+H)+. the flask was cooled in an ice bath The resulting suspension was stirred overnight filtered The filtrate was partitioned between EtOAc (300 mL) and H2O The layers were separated the aqueous layer was extracted with EtOAc The combined organic layers were dried (Na2SO4) concentrated to dryness

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

Procedure: 4-Pentynoic acid (500 mg, 5.1 mmol), EDCI (1.56 g, 7.7 mmol) and HOBt (1.411 g, 10.2 mmol) were dissolved in 20 mL of DCM under inert atmosphere. A mixture of pyrrolidine (850 uL, 10.2 mmol) and DIPEA (4.5 mL, 25.5 mmol) in 3 mL DCM was added and the mixture was stirred for 2 h. The mixture was quenched with 25 mL 10% citric acid, stirred for 5 min., the organic layer was collected and the aqueous layer was extracted with 2×20 mL DCM. The combined organic layers were washed with 20 mL 10% citric acid. The DCM layer was washed with 20 mL saturated sodium bicarbonate, 20 mL brine and dried over sodium sulfate. The filtrates were concentrated and the residue was adsorbed on silica gel and chromatographed on silica gel (12 g) using 0→20% EtOAc-DCM to give 620 mg of 1-(pyrrolidin-1-yl)pent-4-yn-1-one. was added The mixture was quenched with 25 mL 10% citric acid stirred for 5 min. the organic layer was collected the aqueous layer was extracted with 2×20 mL DCM The combined organic layers were washed with 20 mL 10% citric acid The DCM layer was washed with 20 mL saturated sodium bicarbonate, 20 mL brine dried over sodium sulfate The filtrates were concentrated chromatographed on silica gel (12 g)

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

Procedure: 4-Pentynoic acid (500 mg, 5.1 mmol), EDCI (1.56 g, 7.7 mmol) and HOBt (1.411 g, 10.2 mmol) were dissolved in 20 mL of DCM under inert atmosphere. A mixture of pyrrolidine (850 uL, 10.2 mmol) and DIPEA (4.5 mL, 25.5 mmol) in 3 mL DCM was added and the mixture was stirred for 2 h. The mixture was quenched with 25 mL 10% citric acid, stirred for 5 min., the organic layer was collected and the aqueous layer was extracted with 2×20 mL DCM. The combined organic layers were washed with 20 mL 10% citric acid. The DCM layer was washed with 20 mL saturated sodium bicarbonate, 20 mL brine and dried over sodium sulfate. The filtrates were concentrated and the residue was adsorbed on silica gel and chromatographed on silica gel (12 g) using 0→20% EtOAc-DCM to give 620 mg of 1-(pyrrolidin-1-yl)pent-4-yn-1-one. was added The mixture was quenched with 25 mL 10% citric acid stirred for 5 min. the organic layer was collected the aqueous layer was extracted with 2×20 mL DCM The combined organic layers were washed with 20 mL 10% citric acid The DCM layer was washed with 20 mL saturated sodium bicarbonate, 20 mL brine dried over sodium sulfate The filtrates were concentrated chromatographed on silica gel (12 g)