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25th July 2012 @ 23:57
Reaction successful (approx 30% yield) but the the product is not quite as pure original. Probably best to keep to carry out the reaction at room temperature or under.

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Cyclodehydration of PMY 57-2 using XtalFluor-E in 1,2-DCE and subsequent oxidation to the oxazole.

PMY58-1.png

Reaction Start Time: 15.00 25/07/12
PMY 57-2 (1.00 g, 3.0 mmol, 1 equiv.) was stirred in 1,2-DCE (40 mL). XtalFluor-E (1.40 g, 6.0 mmol, 2 equiv.) was added and the reaction heated to 90 °C under nitrogen. After 18 hours, reaction is complete by TLC. The reaction was cooled to room temperature and a solution Na2CO3 (1:1 saturated soln/water, approx 30 mL) was added. The reaction was stirred for 10 minutes, then separated. The aqueous layer was extracted with DCM (3 × 20 mL). The combined organic extracts were washed with brine then dried (MgSO4) and concentrated to a brown foam (1.04 g, 110% of theory). 1H NMR consistent with PMY 58-1 intermediate.

13.40 26/07/12 The intermediate was dissolved in DCM (50 mL). DBU (1.3 mL, 8.7 mmol, 2.9 equiv.) and bromotrichloromethane (0.88 mL, 8.9 mmol, 3.0 equiv.) were added. The reaction was heated to reflux. TLCs show reaction progress. At 3.5 hrs, a new product spot was observed. Reaction cooled to 25 °C for overnight reaction. After overnight reaction, TLC shows consumptions of SM and some impurities. The reaction was concentrated under reduced pressure and purified by chromatography on silica (5-20% acetone/hexane). Long drawn out product spot, late and early running impurities not observed. PMY 58-2 (322 mg, 34%), slightly yellow solid consistent with PMY 58-1 by TLC. Column flush using 5% MeOH/DCM brought out impurities, brown solid (192 mg).

TLC (5% MeOH/DCM) visualised with UV and vanillin:
TLC stage 1
TLC stage 2, 0.5 hours
TLC stage 2, 1.5 hrs
TLC stage 2, 3.5 hours
TLC overnight


NMR:
1H NMR intermediate
1H NMR PMY 58-2


50% acetone/hexane
Column TLC, 20% acetone/hexane

20% acetone/hexane
58-2 vs 58-1, acetone/hexane


See also:
Scaled-up coupling of pyrrole acid chloride and serine methyl ester (PMY 57-2)
Cyclodehydration of carboxamide PMY 57-1 (PMY 58-1)
Coupling of pyrrole acid chloride and serine methyl ester (PMY 57-1)
Synthesis of aryl pyrrole oxazole ester from aldehyde and Serine methyl ester (PMY 46-1)
Synthesis of aryl pyrrole oxazole ester (PMY 45-1)

Risk and Hazard Assessment:
RA
Linked Posts
Attached Files
TLC stage 1
TLC stage 2, 0.5 hours
TLC stage 2, 1.5 hrs
TLC stage 2, 3.5 hours
TLC overnight
58-2 vs 58-1, acetone/hexane
Column TLC, 20% acetone/hexane
1H NMR PMY 58-2
1H NMR intermediate