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24th September 2012 @ 04:11
Eschweiler-Clarke methylation of 1-amino-2-methyl-1-oxopropan-2-yl 1-(4-fluorophenyl)-2,5-dimethyl-1H-pyrrole-3-carboxylate to give 1-(dimethylamino)-2-methyl-1-oxopropan-2-yl 1-(4-fluorophenyl)-2,5-dimethyl-1H-pyrrole-3-carboxylate as an analogue of MD 5-1.

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Reaction start time: EST 24/9/12

See also:

Risk and Hazard assessment:
RA
Attached Files
23rd September 2012 @ 23:22
1-amino-2-methyl-1-oxopropan-2-yl 1-(4-fluorophenyl)-2,5-dimethyl-1H-pyrrole-3-carboxylate (MD 5-2) was synthesised (0.64 g, 2.0 mmol, 47% yield).

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Upscaled synthesis of OSDD desired synthetic compound, 1-amino-2-methyl-1-oxopropan-2-yl 1-(4-fluorophenyl)-2,5-dimethyl-1H-pyrrole-3-carboxylate.

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Reaction start time: 5:00 PM EST 13/9/12

MD 2-1 (1 g, 4.3 mmol, 1 equiv) and 2-Bromo-2-methylpropionamide (1.4 g, 8.5 mmol, 2 equiv) were dissolved in a acetonitrile and water mixture (17 mL, 95:5). Silver Oxide (2.0 g, 8.5 mmol, 2 equiv) was added and the reaction was left at room temperature covered in aluminium foil for 18 hours.

The reaction was filtered through cellite with methanol and the filtrate was concentrated under reduced atmosphere the give the crude product (0.81 g, light orange powdery solid). The crude solid was columned (50:50 hexane:EtOAc) to give the pure product (0.64 g, 2.0 mmol, 47% yield).

The product was characterised by 1H and 13 NMR and matched the spectra of MD 5-1.

See also:
Synthesis of 1-amino-2-methyl-1-oxopropan-2-yl 1-(4-fluorophenyl)-2,5-dimethyl-1H-pyrrole-3-carboxylate MD (5-1)

Risk and Hazard assessment:
Same as MD 5-1
Linked Posts
20th September 2012 @ 04:22
Upscaled synthesis of sodium 1-(4-fluorophenyl)-2,5-dimethyl-1H-pyrrole-3-sulfonate for further synthesis into a sulfonamide.

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Reaction start time: 11:30 AM EST 20/9/12
Ethyl 1-(4-fluorophenyl)-2,5-dimethyl-1Hpyrrole (0.75 g, 4.0 mmol, 1 equiv) and Sulfur trioxide pyridine (1.9 g, 12 mmol, 3 equiv) were refluxed in toluene (6 mL) for 20 hours.

The toluene was then decanted out and water (10 mL) was added to the solid, followed by heating. To the boiling solution Sodium Carbonate (2 g) was added. The solution was concentrated under reduced atmosphere to give a crude brown and white precipitate. The product was extracted by boiling the crude precipitate in a water:ethanol (20 mL, 10:90) solution for 1 hour followed by filtration. The filtrate was left to cool to room temperature at which point precipitate formed. The precipitate was filtered and washed with ethanol leaving white, powdery solid behind (1.0 g, 86% yield, 3.4 mmol).

See also:
Method used from this paper
Synthesis of sodium 1-(4-fluorophenyl)-2,5-dimethyl-1H-pyrrole-3-sulfonate (MD 6-1)

Risk and Hazard assessment:
Same as MD 6-1 except increased quantities of reagents
Linked Posts
10th September 2012 @ 01:56
Synthesis of sodium 1-(4-fluorophenyl)-2,5-dimethyl-1H-pyrrole-3-sulfonate for further synthesis into a sulfonamide.

3118.png

Reaction start time: 11:30 AM EST 10/9/12
Ethyl 1-(4-fluorophenyl)-2,5-dimethyl-1Hpyrrole ( 0.095 g, 0.5 mmol, 1 equiv) and Sulfur trioxide pyridine ( 0.24 g, 1.5 mmol, 3 equiv) were refluxed in toluene (1 mL) for 24 hours. Remaining solvent was decanted. To the remaining solid, water (5 mL) was added and brought to the boil followed by sodium carbonate (5 g). The crude product was concentrated under reduced atmosphere, leaving brown and white solids.

A HNMR and CNMR of the crude product showed that some starting material had been sulfonated at the 3 position while others had been sulfonated at both the 3 and 4 positions on the pyrrole ring. The product was not further purified and instead the reaction was redone on a larger scale.

See also:
Method used from this paper
Repeat Preparation of 1-(4-Fluoro-phenyl)-2,5-dimethyl-1H-pyrrole (AEW 1-1)
Scale-up (100 mmol) of Paal-Knorr Synthesis of 1-aryl-2,5-dimethyl Pyrrole Core (PMY 1-6)
Synthesis of sodium 1-(4-fluorophenyl)-2,5-dimethyl-1H-pyrrole-3-sulfonate (MD 6-2)

Risk and Hazard assessment:
MD 6-1 RA
Linked Posts
Attached Files
4th September 2012 @ 23:11
Synthesis of 1-ethoxy-2-methyl-1-oxopropan-2-yl 1-(4-fluorophenyl)-2,5-dimethyl-1H-pyrrole-3-carboxylate from MD 2-1 to show that the Silver Oxide reaction works.

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Reaction start time: 9:40 AM EST 5/9/12
MD 2-1 (0.24g, 1 mmol, 1 equiv) was dissolved in an acetonitrile/water mixture (95:5, 5 mL). Methyl 2-bromo-2-methylpropionate (260 μL, 2 mmol, 2 equiv) was then added to the mixture followed by Ag2O (0.45 g, 2 mmol, 2 equiv). The reaction was left for 4 hours at room temperature covered in Aluminium foil to keep light out as that may be why it didn't work previously.

See also:
Synthesis of 1-ethoxy-2-methyl-1-oxopropan-2-yl 1-(4-fluorophenyl)-2,5-dimethyl-1H-pyrrole-3-carboxylate (MD 3-3)

Risk and Hazard assessment:
Same as MD 3-3
Linked Posts