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19th October 2012 @ 01:50
Reaction successful, 51% yield over 2 steps. Product progressed to acid in PMY 59-3

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Cyclodehydration of PMY 67-1 using XtalFluor-E in 1,2-DCE and subsequent oxidation to the oxazole.

PMY58-1.png

Reaction Start Time: 11.40 19/10/12
PMY 57-1 (509 mg, 1.52 mmol, 1 equiv.) was stirred in 1,2-DCE (20 mL). XtalFluor-E (697 mg, 3.04 mmol, 2 equiv.) was added and the reaction heated to 90 °C. After 80 minutes, TLC shows reaction essentially complete. The reaction was cooled to room temperature and saturated K2CO3(aq) and water (1:1, 20 mL) were added. After stirring vigorously for 5 minutes, the layers were separated and the aqueous layer extracted with DCM (3 × 10 mL). The combined organic layers were washed with water, brine then dried (MgSO4) and concetrated under reduced pressure to a brown oil (563 mg, 117% of theory). Purified by chromatography on silica (20-50% EtOAc/hexane) to give pale brown viscous oil (360 mg, 74% of theory). Consistent with intermediate obtained in PMY 58-1 + residual solvents.

09.40 23/10/12 Intermediate was dissolved in DCM (10 mL) and DBU (0.51 mL, 3.4 mmol, 3 equiv.) and bromotrichloromethane (0.34 mmol, 3.4 mmol, 3 equiv.) were added. The mixture was heated to reflux. After 80 minutes, TLC shows formation of product and SM. Reaction not complete after 7 hours. Left overnight. Reaction not complete by TLC. Concentrated to viscous brown oil which was purified by chromatography on silica (10-18% acetone/hexane) to give a white crystalline solid (244 mg, 68%). Some SM and mixed fractions also obtained.

TLC (5% MeOH/DCM) visualised with UV and vanillin:
TLC 80 mins
TLC stage 2


NMR:
1H NMR intermediate
1H NMR step 2


See also:
Coupling of pyrrole acid and serine methyl ester (PMY 67-1)
Scaled-up cyclodehydration of carboxamide PMY 57-2 (PMY 58-2)
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)

Reference:
doi:10.1016/j.tetlet.2012.05.130

Risk and Hazard Assessment:
See: Cyclodehydration of carboxamide PMY 57-1 (PMY 58-1)
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Attached Files
TLC 80 mins
1H NMR intermediate
TLC stage 2
1H NMR step 2
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