All Notebooks | Help | Support | About
4th October 2011 @ 02:23
===

Coupling of carboxylic acid PMY 8-2 with side chain PMY 9-1 using carbodiimide coupling in presence of catalytic DMAP.

Reaction Scheme

Reaction start time: 16.30 05/10/11
PMY 8-2 (100 mg, 0.43 mmol, 1 equiv.), PMY 9-1, dried under vacuum prior to reaction (123 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. After 17 hours, TLC shows consumption of SM, formation of product and "anhydride". Reaction 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 concentration and trituration/filtration (EtOAc) did not completely remove urea. Not as clean as before.. Probably best to switch to EDC or CDI other water soluble coupling reagent

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

Left to right: PMY 8-2 (recrystallised), PMY 8-2/RM, RM, RM/PMY 11-2, PMY 11-2 (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.
Linked Posts
Attached Files
Reaction Scheme
TLC 17 hours
1H, 13C, 19F NMR. Contains urea by product
1H NMR filtered
Comments