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21st October 2012 @ 08:18
Coupling of the recrystallised pyrazole carboxylic acid MJT 3-2 with serine methyl ester using N-(3-Dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride and hydroxybenzotriazole.

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Reaction start time: 1510 22-10-2012

MJT 3-2 (1.257 g, 5.7 mmol, 1 equiv.) was stirred in DCM (40 mL), cloudy solution, kept under nitrogen atmosphere. EDCI (1.20 g, 6.3 mmol, 1.1 equiv.) and HOBt (0.085 g, 0.63 mmol, 0.11 equiv.) were added. DIPEA (2.2 mL, 12.6 mmol, 2.2 equiv.) was added, insoluble at first. Solution stirred for ten minutes and DIPEA dissolved. Serine methyl ester hydrochloride (0.977 g, 6.3 mmol, 1.1 equiv.) to give a colourless solution. Mixture stirred overnight at room temperature.

1030AM 23-10-12.
After 19 hours mixture is a colourless solution with some white solid stuck to sides of vessel. TLC shows some starting material (pyrazole carboxylic acid) remains and formation of a product slightly more polar than this starting material as well as multiple more polar products.
NH4Cl (20 mL) is added to the reaction mixture and then HCl (1M) is added until solution is pH 1. The organic layer was then extracted and washed with water (3 x 20 mL), Na2CO3 (20 mL), water (3 x 20 mL) and finally brine (20 mL) before being dried over MgSO4 and concentrated to a white foam (0.5492 g). TLC analysis shows no SM remains and that three products are present, least polar of highest intensity under UV. NMR analysis consistent with expected product but with minor impurities.

12PM 24-10-12
Crude product is purified by column chromatography (5%; 10% MeOH / DCM) to give MJT 5-1 as a white foam (0.44 g, 1.44 mmol, 25%). NMR analysis consistent with expected product.
ca. 50 mg is retained for characterisation.
This is a novel compound

TLC (10 % MeOH / DCM) visuallised with UV then vanillin stain
before workup
TLC after workup


NMR
nmr data crude
crude material NMR pdf


Hazard and risk assessment
HIRAC MJT5-1.pdf


References

EDC Coupling of Pyrrole Carboxylic acid with Hydrazine Hydrate (AEW 14-2)
Hydrolysis of Ethyl 1-(4-fluorophenyl)-5-methyl-1H-pyrazole-4-carboxylate (MJT 3-2)
Linked Posts
Attached Files
5-1 scheme
HIRAC MJT5-1.pdf
amended scheme with serine methyl ester
amended scheme with serine methyl ester
nmr data crude
crude material NMR pdf
before workup
TLC after workup