TCMDC_ArylPyrrole

 

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Conversion of carboxylic acid PMY 8-2 to the acid chloride using thionyl chloride and its subsequent coupling with glycolamide to give TCMDC-123812.




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, mixture concentrated under reduced pressure, redissolved in toluene and concentrated twice more.

Residue dissolved in MeCN (5 mL). Glycolamide (37 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). Brown oil (40 mg, 31% of theory) consistent with expected product by ¹H NMR and impurities. Also recovered mixture of SM and "anhydride" (46 mg). Recolumned (0-3% MeOH/DCM, careful) to obtain crystalline pale brown solid (27.3 mg).

m/z (ESI+) 313 [M+Na]⁺

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/glycolamide, glycolamide.



NMR:


Repurified:



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 11-2)
Synthesis of TCMDC-123794 via acid chloride (PMY 11-1)

Identifiers:
InChi: InChI=1S/C15H15FN2O3/c1-9-7-13(15(20)21-8-14(17)19)10(2)18(9)12-5-3-11(16)4-6-12/h3-7H,8H2,1-2H3,(H2,17,19)
SMILES: Cc1cc(C(=O)OCC(N)=O)c(C)n1-c1ccc(F)cc1
Name: carbamoylmethyl 1-(4-fluorophenyl)-2,5-dimethyl-1H-pyrrole-3-carboxylate
ChemDraw name: 2-amino-2-oxoethyl 1-(4-fluorophenyl)-2,5-dimethyl-1H-pyrrole-3-carboxylate