TCMDC_ArylPyrrole

 

Conversion of carboxylic acid PMY 8-2 to the acid chloride using thionyl chloride and its subsequent coupling with side chain PMY 9-1 to give TCMDC-123794.



Reaction start time: 16.20 EST 26/09/11
PMY 8-2 (104 mg, 0.45 mmol, 1 equiv.) was dissolved in dry PhMe (5 mL). 1 drop DMF added followed by thionyl chloride (0.2 mL, 2.74 mmol, 6 equiv.). After 2 hours, TLC does not show product consistant with PMY 10/11-1. Mixture concentrated under reduced pressure, redissolved in toluene and concentrated twice more.

Residue dissolved in MeCN (5 mL). Side chain PMY 9-1 (131 mg, 0.50 mmol, 1.1 equiv.) in MecN (2 mL) and triethylamine (0.2 mL) was added and the reaction heated to 60 °C overnight. After 15 hours, TLC shows formation of products and starting materials and impurity consistant with PMY 10/11-1 (suspect anhydride of acid SM). Reaction cooled and then concentrated under reduced pressure. The residue was purified by chromatography on silica (10-50% EtOAc/petrol, then 3-10% MeOH/DCM) to obtain a brown glassy oil after drying under vacuum (49 mg, 23% of theory, not clean). Recovered SM mixed with "anhydride" (60 mg) and a polar gum (110-140 mg, side chain by TLC). The gum was subjected to high vacuum with gentle heating to drive off solvent. A white material sublimed onto the flask, NMR attached). glassy oil repurified by chromatography (0-3% MeOH/DCM) to obtain a clear glass (17 mg)

TLC (25% EtOAc/petrol) visualised with UV and vanillin:


Left to right: 1:1, 3:1 EtOAc/petrol, 10% MeOH/DCM, 10% MeOH/DCM. Plate on far right spots as follows: PMY 8-2, reaction mix (RM)/PMY 8-2, RM, RM/PMY 9-1, PMY 9-1. A bit sideways on the final plate too, due to a drop of solvent high up on the plate.

NMR:



IR:


Mass Spectrometry:
m/z (ESI+) 477 [M+H]⁺

Risk and Hazard Assessment:
See: Synthesis of TCMDC-123812 via acid chloride (PMY 10-1)

See also:
Synthesis of TCMDC-123794 via acid chloride (PMY 11-1)
Synthesis of TCMDC-123812 via acid chloride (PMY 10-2)