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30th May 2013 @ 18:19

 

375 mg of 4-fluorophenyl azide (2 mmol) and 127 mg of methyl propynyloxyacetate (1 mmol) were dissolved in DCM:H2O (3ml:2ml) and stirred overnight with copper sulfate (12 mg) and sodium ascorbate (20 mg). The mixture was diluted with DCM and the organic layer washed with water, dried over magnesium sulfate and concentrated in vacuo to give 272 mg of yellow solid which was purified by dry column vacuum chromatography (40% ethyl acetate in heptane, followed by 100% ethyl acetate after 20 fractions) to give 4 products:

 

 

C1, 8.6 mg orange waxy solid. Inconsistent mass spec data.

PT-1-14-C1 1H.pdf
PT-1-14-C1 13C.pdf
PT-1-14-C1 DEPT135.pdf
PT-1-14-C1 DEPT90.pdf

 

 

C2, 42.3 mg (15%) white solid ESI-Nom 302 (M+Na)+, 581 (2M+Na) HRMS consistent

PT-1-14-C2 1H.pdf
PT-1-14-C2 13C.pdf
PT-1-14-C2 DEPT135.pdf
PT-1-14-C2 DEPT90.pdf
PT-1-14-C2 ESI-MS.jpg
PT-1-14-C2 HRMS.pdf

 

 

C3, desired product, white solid, 44.7 mg (17%) ESI-Nom 288 (M+Na+), 553 (2M+Na) HRMS consistent

PT-1-14-C3 1H.pdf
PT-1-14-C3 13C.pdf
PT-1-14-C3 DEPT135.pdf
PT-1-14-C3 DEPT90.pdf
PT-1-14-C3 ESI-MS.jpg
PT-1-14-C3 HRMS.pdf

 

 

C4, 18.6 mg (4%) white solid ESI-Nom 449 (M+Na+), 875 (2M+Na) HRMS consistent

PT-1-14-C4 1H.pdf
PT-1-14-C4 13C.pdf
PT-1-14-C4 DEPT135.pdf
PT-1-14-C4 DEPT90.pdf
PT-1-14-C4 ESI-MS.jpg
PT-1-14-C4 HRMS.pdf

 

Results and discussion.

C1, C3, and C4 seemingly correspond to the three possible products of the previous reaction and are present due to insufficient purification of PT-1-13 shown here:

Products.png

 C2 has apparently been produced by trans-esterification with ethanol even though no ethanol was used at any point.

The Mass Spectroscopy evidence for C1 is extremely unreliable, but the NMR evidence fits extremely well with analagous chemical shifts for CH2 groups in similar environments in product C4 (triazole-CH2-ester) and methyl bromoacetate (Br-CH2-ester). DEPT is consistent but there isn't enough sample to identify all the quaternary carbons - requires further study if it's a compound of interest.

C1-C4 have all been sent for antimalarial screening.

 

 

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30th May 2013 @ 05:59

Repeated to collect data for paper - see original experiment Reductive amination of pyrrole aldehyde with crude PMY 53-2 (PMY 56-1)


PMY 2-5 (91 mg, 0.42 mmol, 1 equiv.) and crude PMY 53-2 (37 mg, ~0.42 mmol) were dissolved in MeOH (5 mL) and acetic acid (0.13 mL) and stirred for 1 hour at room temperature. Sodium cyanoborohydride (37 mg, 1.01 mmol, 1.1 equiv.) was added. After 1 hour, no product was observed by TLC. Reaction mixture was stirred for 20 hours and no product spot observed by TLC.

Volatiles were removed in vacuo and then 1M NaOH added and the mixture extracted with CH2Cl2, organic layer washed with brine, dried (MgSO4), filtered and evaporated to give a pale brown oil.

Crude indicated desired product - Purified by flash column (1-15% MeOH) no product recovered.

 

Data:

AEW 60-1 crude.zip
Attached Files
30th May 2013 @ 00:46

Repeated to collect data for paper - see original experiment Coupling of pyrrole acid chloride PMY 32-2 and glycinamide (PMY 31-5) but attempted with EDCI and HOBt for convenience.

Procedure:

AEW 10-1 (51 mg, 0.22 mmol, 1 equiv.) was dissolved in CH2Cl2 (2.2 mL) under Argon. EDC (51 mg, 0.26 mmol, 1.2 equiv.) and HOBt (3 mg, 0.02 mmol. 0.1 equiv.) were added and the yellow solution stirred at room temperature for 15 minutes under Argon. Glycinamide hydrochloride (24 mg, 0.22 mmol, 1 equiv.) was added and the reaction mixture stirred at room temperature . No product observed after 1 h or 20 h. DIPEA (0.09 mL, 0.15 mmol, 2.3 equiv.) was added and the white globules in the orange solution dispersed and a white solid crashed out of the mixture. Reaction mixture left to stir at room temperature o/n. Possible roduct observed by TLC. Work up CH2Cl2 and a saturated aqueous solution of NaHCO3, brine, MgSO4, filtered and evaporated.

CH2Clbottle did not contain CH2Cl2!! but seemingly strong acid! 1H NMR consequently shows some decomposition: reaction thrown in waste.

Data:

 

Hazard and Risk Assessment:

See: Amidation of pyrrole acid with dimethylamine (AEW 16-1) and Coupling of pyrrole acid chloride PMY 32-2 and glycinamide (PMY 31-5)

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