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5th December 2011 @ 05:14
=== Coupling of carboxylic acid [url=]PMY 8-2[/url] with [url=]glycolamide[/url] using propylphosphonic anhydride ( ([url=]T3P[/url]) and pyridine in ethyl acetate. Attempt to optimise coupling conditions. Method based on reference shown below. [b]Reaction start time: 15.30 05/12/11[/b] PMY 8-3 (50 mg, 0.21 mmol, 1 equiv.), glycolamide (18 mg, 0.24 mmol, 1.1 equiv.) were dissolved in EtOAc (approx. 1 mL) and DMF (0.2 mL), pyridine (0.1 mL, 1.3 mmol, 6 equiv.) and cooled in salt/ice. T3P 50% in EtOAc (0.26 mL, 0.43 mmol, 2 equiv.) was added dropwise over 3 minutes. 4-DMAP (a few crystals) were added as a solution in EtOAc (0.5 mL) and the reaction allowed to warm to room temperature overnight. After 17 hours, 0.5M HCl (4 mL) was added. The mixture was stirred for approx 1.5 hours. The mixture was diluted with EtOAc (approx 10 mL) and the layers were then separated and the organic washed again with 0.5M HCl (10 mL) followed by brine, then dried (MgSO4) and concentrated to a dark brown solid. 1H NMR shows mostly SM acid and a new product not consistent with desired product. The side reaction signals were observed in the crude mixture in PMY 10-2. [b]TLC (10% MeOH/DCM) visualised with UV and vanillin:[/b] [data]908[/data] [b]NMR:[/b] [data]880[/data] [b]Risk and Hazard Assessment:[/b] See: [blog]367[/blog] Propylphosphonic anhydride is corrosive [b]Reference:[/b] DOI:[url=]10.1021/ol201875q[/url] See also: [blog]601[/blog] [blog]542[/blog] [blog]499[/blog]
Attached Files
Reaction Scheme
1H NMR crude
TLC before quench