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4th October 2011 @ 23:35
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Coupling of carboxylic acid PMY 8-2 with glycolamide using carbodiimide coupling in presence of catalytic 4-DMAP.

Reaction Scheme

Reaction start time: 16.30 04/10/11
PMY 8-2 (100 mg, 0.43 mmol, 1 equiv.), glycolamide (35 mg, 0.47 mmol, 1.1 equiv.),4-DMAP (approx 10 mg, 20%) were stirred in DCM (10 mL). Diisopropylcarbodiimide (0.08 mL, 0.51 mmol, 1.2 equiv.) was added and the reaction stirred at room temperature for 17 hours. TLC shows consumption of starting material, formation of product and "anhydride". After 40 hours, no change on TLC. "Anhydride" not converted to product. Reaction mixture concentrated under a stream of nitrogen. Purified by chromatography on silica (0-5% MeOH/DCM) to obtain a light brown solid with white crystals. 1H NMR consistent with product and diisopropyl urea. Further trituration/filtration (EtOAc) did not remove urea, product not as clean as before. As for PMY 11-3, maybe use EDC.

TLC (10% MeOH/DCM) visualised with UV and vanillin:
TLC 17 hours
TLC 40 hours

Left to right: PMY 8-2 (recrystallised), PMY 8-2/RM, RM, RM/PMY 10-2, PMY 10-2 (product).

NMR:
1H, 13C, 19F NMR. Contains urea by product
1H NMR filtered


Risk and Hazard Assessment:
For coupling reagent hazards see: Synthesis of TCMDC-123794 Side-chain (PMY 5-1)
Additional hazard; treat product as toxic.
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Reaction Scheme
TLC 17 hours
TLC 40 hours
1H, 13C, 19F NMR. Contains urea by product
1H NMR filtered
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