TCMDC_ArylPyrrole

 

Product obtained in 52% yield.

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Coupling of hippuric acid and 4-aminoantipyrine using T3P to obtain the glycine benzamide.



Reaction start time: 16.30 08/12/11
Hippuric acid PMY 26-1 (200 mg, 1.12 mmol, 1 equiv.) and 4-aminoantipyrine (250 mg, 1.23 mmol, 1.1 equiv.) were dissolved in pyridine (1 mL) and DMF (1 mL) and cooled in ice/water. 50% T3P in EtOAc (1 mL, 1.7 mmol, 1.5 equiv.) was added after 30 minutes, the reaction was allowed to warm to room temperature and the reaction stirred for 16 hours. 0.5M HCl (10 mL) and EtOAc (10 mL) were added. After approx 10 minutes of stirring, copious white precipitate formed. Cooled in ice then filtered, white solid washed with water. Filtrate (pH 4) was separated and the organic layer washed with 5% NaOH (10 mL), water (3 × 10 mL), brine then dried (MgSO₄) and concentrated to a orange solid, PMY 27-1-B (24 mg). TLC shows white solid and orange gum to be new products. White solid dried under vacuum, PMY 27-1-A (211 mg, 52%). 27-1-A is consistent with expected product by ¹H NMR.

PMY 27-1-A solubility:
DCM (reasonably), acetone (sparingly), EtOAc (sparingly), water (insoluble), [from reaction DMF (readily)].

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

TLC before quench. Left to right: PMY 26-1 in DMF, mix, reaction mixture, 4-aminoantipyrine.


Left to right: white solid, mix, PMY 26-1 (loaded in acetone), 4-aminoantipyrine, mix, orange solid.


(12% MeOH/DCM) Left to right: white solid, mix, 4-aminoantipyrine, mix, orange solid, mix, PMY 26-1.

NMR:


Risk and Hazard Assessment:
As for, Synthesis of TCMDC-123812 using T3P (PMY 10-4)

See also:
Synthesis of hippuric acid (PMY 26-1)

References:
In addition to reference also

10.1021/op900178d