2-prop-2-ynylpent-4-ynoic acid

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-boc-ethylenediamine (18.3 gm, 0.1143 mol) in 50 ml of CH3CN was added slowly via an addition funnel to a stirred solution containing dipropargylacetic acid (15.56 gm, 0.1143 mol), TBTU (36.74 gm, 0.114 mol) and DIPEA (29.6 gm, 0.229 mol) in 300 ml of CH3CN at 0 C. Precipitation occurred. The ice bath was removed and the product was stirred at ambient temperature overnight (16 hours). The reaction was now totally homogeneous. The solution was concentrated in vacuo and the residue was diluted with 800 ml of water. The resulting solids were filtered, washed copiously with water, and vacuum dried to give 14.3 gm of crude product. Re-crystallization (2×) from DCM, filtration and washing with hexanes affords the product (9.85 gm, 31% yield, 98% purity by HPLC (214 nm)). Precipitation The ice bath was removed The solution was concentrated in vacuo the residue was diluted with 800 ml of water The resulting solids were filtered washed copiously with water, and vacuum dried

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The dipropargylmalonic acid (26 gm, 0.443 mol) was heated neat at 135 C until CO2 stopped evolving. It was then allowed to cool to an oil. The oil was distilled at 0.5 psi. The remaining oily residue in the distillation flask and solid were combined (15.7 gm, 79.9% yield) and was used as is in the next step. to cool to an oil The oil was distilled at 0.5 psi

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The dipropargylmalonic acid (26 gm, 0.443 mol) was heated neat at 135 C until CO2 stopped evolving. It was then allowed to cool to an oil. The oil was distilled at 0.5 psi. The remaining oily residue in the distillation flask and solid were combined (15.7 gm, 79.9% yield) and was used as is in the next step. to cool to an oil The oil was distilled at 0.5 psi

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-boc-ethylenediamine (18.3 gm, 0.1143 mol) in 50 ml of CH3CN was added slowly via an addition funnel to a stirred solution containing dipropargylacetic acid (15.56 gm, 0.1143 mol), TBTU (36.74 gm, 0.114 mol) and DIPEA (29.6 gm, 0.229 mol) in 300 ml of CH3CN at 0 C. Precipitation occurred. The ice bath was removed and the product was stirred at ambient temperature overnight (16 hours). The reaction was now totally homogeneous. The solution was concentrated in vacuo and the residue was diluted with 800 ml of water. The resulting solids were filtered, washed copiously with water, and vacuum dried to give 14.3 gm of crude product. Re-crystallization (2×) from DCM, filtration and washing with hexanes affords the product (9.85 gm, 31% yield, 98% purity by HPLC (214 nm)). Precipitation The ice bath was removed The solution was concentrated in vacuo the residue was diluted with 800 ml of water The resulting solids were filtered washed copiously with water, and vacuum dried

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The dipropargylmalonic acid (26 gm, 0.443 mol) was heated neat at 135 C until CO2 stopped evolving. It was then allowed to cool to an oil. The oil was distilled at 0.5 psi. The remaining oily residue in the distillation flask and solid were combined (15.7 gm, 79.9% yield) and was used as is in the next step. to cool to an oil The oil was distilled at 0.5 psi

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-boc-ethylenediamine (18.3 gm, 0.1143 mol) in 50 ml of CH3CN was added slowly via an addition funnel to a stirred solution containing dipropargylacetic acid (15.56 gm, 0.1143 mol), TBTU (36.74 gm, 0.114 mol) and DIPEA (29.6 gm, 0.229 mol) in 300 ml of CH3CN at 0 C. Precipitation occurred. The ice bath was removed and the product was stirred at ambient temperature overnight (16 hours). The reaction was now totally homogeneous. The solution was concentrated in vacuo and the residue was diluted with 800 ml of water. The resulting solids were filtered, washed copiously with water, and vacuum dried to give 14.3 gm of crude product. Re-crystallization (2×) from DCM, filtration and washing with hexanes affords the product (9.85 gm, 31% yield, 98% purity by HPLC (214 nm)). Precipitation The ice bath was removed The solution was concentrated in vacuo the residue was diluted with 800 ml of water The resulting solids were filtered washed copiously with water, and vacuum dried

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The dipropargylmalonic acid (26 gm, 0.443 mol) was heated neat at 135 C until CO2 stopped evolving. It was then allowed to cool to an oil. The oil was distilled at 0.5 psi. The remaining oily residue in the distillation flask and solid were combined (15.7 gm, 79.9% yield) and was used as is in the next step. to cool to an oil The oil was distilled at 0.5 psi

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-boc-ethylenediamine (18.3 gm, 0.1143 mol) in 50 ml of CH3CN was added slowly via an addition funnel to a stirred solution containing dipropargylacetic acid (15.56 gm, 0.1143 mol), TBTU (36.74 gm, 0.114 mol) and DIPEA (29.6 gm, 0.229 mol) in 300 ml of CH3CN at 0 C. Precipitation occurred. The ice bath was removed and the product was stirred at ambient temperature overnight (16 hours). The reaction was now totally homogeneous. The solution was concentrated in vacuo and the residue was diluted with 800 ml of water. The resulting solids were filtered, washed copiously with water, and vacuum dried to give 14.3 gm of crude product. Re-crystallization (2×) from DCM, filtration and washing with hexanes affords the product (9.85 gm, 31% yield, 98% purity by HPLC (214 nm)). Precipitation The ice bath was removed The solution was concentrated in vacuo the residue was diluted with 800 ml of water The resulting solids were filtered washed copiously with water, and vacuum dried

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: The dipropargylmalonic acid (26 gm, 0.443 mol) was heated neat at 135 C until CO2 stopped evolving. It was then allowed to cool to an oil. The oil was distilled at 0.5 psi. The remaining oily residue in the distillation flask and solid were combined (15.7 gm, 79.9% yield) and was used as is in the next step. to cool to an oil The oil was distilled at 0.5 psi

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a solution of 2-(2-propynyl)-4-pentynoic acid 42 (25.0 g, 0.184 mol) in toluene (200 ml) was added triethylamine (19.5 g, 0.193 mol) with cooling. Diphenylphosphoryl azide (50.5 g, 0.184 mol) was added, and the mixture was stirred at room temperature for 15 minutes. The mixture was heated on the steam bath until the reaction became exothermic. When the reaction subsided, the heating was continued for an additional 10 minutes during which time the evolution of gas ceased. Dry t-butanol (150 ml) was added, and the mixture was heated at reflux on the steam bath for 24 hours. The solvent was removed under vacuum, and the residue was diltued with water and extracted twice with diethylether. The combined aqueous extracts were washed with water (2×), 10% sodium carbonate solution, and brine. The solution was dried (MgSO4), and the solvent was removed under vacuum to leave crude 43 as a red-brown solid (35.35 g). A sample (3.2 g) was purified via flash chromatography (230-400 mesh silica gel, 10% ethyl acetate in hexane) to give a colorless solid (2.69 g). Crystallization from hexane gave the title compound (43) as colorless crystals (m.p. 64-67° C.). with cooling The mixture was heated on the steam bath until the reaction the heating was continued for an additional 10 minutes during which time the mixture was heated at reflux on the steam bath for 24 hours The solvent was removed under vacuum extracted twice with diethylether The combined aqueous extracts were washed with water (2×), 10% sodium carbonate solution, and brine The solution was dried (MgSO4) the solvent was removed under vacuum

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Methyl 2-(2-propynyl)-4-pentynoate (27.5 g) was saponified with sodium hydroxide (22 g) in refluxing water (250 ml). The solution was cooled and acidified with 12 N HCl to pH 3, and then extracted with t-butyl methyl ether. The organic layer was washed with brine and dried over sodium sulfate. Solvent removal afforded the title compound. The solution was cooled extracted with t-butyl methyl ether The organic layer was washed with brine dried over sodium sulfate Solvent removal

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: N-boc-ethylenediamine (18.3 gm, 0.1143 mol) in 50 ml of CH3CN was added slowly via an addition funnel to a stirred solution containing dipropargylacetic acid (15.56 gm, 0.1143 mol), TBTU (36.74 gm, 0.114 mol) and DIPEA (29.6 gm, 0.229 mol) in 300 ml of CH3CN at 0 C. Precipitation occurred. The ice bath was removed and the product was stirred at ambient temperature overnight (16 hours). The reaction was now totally homogeneous. The solution was concentrated in vacuo and the residue was diluted with 800 ml of water. The resulting solids were filtered, washed copiously with water, and vacuum dried to give 14.3 gm of crude product. Re-crystallization (2×) from DCM, filtration and washing with hexanes affords the product (9.85 gm, 31% yield, 98% purity by HPLC (214 nm)). Precipitation The ice bath was removed The solution was concentrated in vacuo the residue was diluted with 800 ml of water The resulting solids were filtered washed copiously with water, and vacuum dried