TCMDC_ArylPyrrole

 

DMF (5.0 mL) was stirred under a nitrogen atmosphere in an ice-bath. Phosphoryl chloride (1.18 mL, 12.7 mmol, 1.2 equiv.) was added and the reaction stirred for 25 minutes. Reaction still colourless. A solution of pyrrole PMY 1-6 (2.00 g, 10.5 mmol, 1 equiv.) in DMF (5 mL) was added dropwise over 5 minutes. The reaction was removed from the ice-bath and allowed to warm to room temperature. After 50 minutes, reaction was complete by TLC. Poured over ice (100 ml). pH adjusted to 6 (approx. 20% NaOH) and left stirring overnight. In the morning pH was 2. 20% NaOH added until pH 11 and the reaction mixture was left to stir for a further 30 minutes. The solid was filtered and washed with water to form a wet beige paste that was recrystallised from (MeCN/water) to obtain a single crop of tan free-flowing powder (2.07 g, 9.5 mmol, 80% yield). 1H NMR showed an impurity at 4.76 ppm, no further purification was performed and the aldehyde was used in reaction 3-1.

Data:


Original Experiment:
Scale up (11 mmol): Formylation of 1-(4-fluorophenyl)-2,5-dimethyl-1H-pyrrole (PMY 2-4)

Starting material synthesis:
Repeat Preparation of 1-(4-Fluoro-phenyl)-2,5-dimethyl-1H-pyrrole (AEW 1-1)

References:

1. 
   
2. Gangjee, A.; Patel, J.; Kisliuk, R. L.; Gaumont, Y; J. Med. Chem., 1992, 35 (20), 3678–3685. doi:10.1021/jm00098a013
   
   
3. Manetti, F.; Magnani, M.; Castagnolo, D.; Passalacqua, L.; Botta, M.; Corelli, F.; Saddi, M.; Deidda, D; De Logu, A. ChemMedChem, 2006, 1, 973–989. doi: 10.1002/cmdc.200600026
   

Structural Information:
InChI=1S/C12H12FN/c1-9-3-4-10(2)14(9)12-7-5-11(13)6-8-12/h3-8H,1-2H3
gave
InChI=1S/C13H12FNO/c1-9-7-11(8-16)10(2)15(9)13-5-3-12(14)4-6-13/h3-8H,1-2H3

Hazard and Risk Assessment: