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17th July 2012 @ 03:28
Product synthesised in 46% yield over two steps.

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Coupling of pyrrole acid chloride and serine methyl ester (PMY 57-1) for cyclisation to the oxazole.

PMY57-1.png

Reaction Start Time: 12.00 17/07/12
JRC 2-1 (250 mg, 1.07 mmol, 1 equiv.) was stirred in PhMe (2 mL). Thionyl chloride (0.16 mL, 2.14 mmol, 2 equiv.) was added and the mixture stirred at room temperature. After 4 hours, the reaction was concentrated and triturated with hexane (5 mL) and concentrated once more, then dissolved in THF (3 mL).

In a separate vessel, DL-serine methyl ester hydrochloride (183 mg, 1.18 mmol, 1.1 equiv.) was stirred in THF (10 mL). Insoluble. DIPEA (0.62 mL, 3.54 mmol, 3.3 equiv.) was added. 1700 Acid chloride solution added to the suspension/solution of serine methyl ester. TLC at 16 hours shows reaction complete (relative to acid). Reaction concentrated under reduced pressure. saturated NaHCO3(aq) and water (1:1) were added to the residue and extracted with DCM (3 × 15 mL). The extracts were then washed with brine and dried (MgSO4) and concentrated to a tan foam (241 mg). Purification by chromatography on silica (1-4% MeOH/DCM) gave a mixed fraction, trace SM acid and prod by TLC, PMY 57-1-A (79 mg) and single spot product white foam PMY 57-1-B (87 mg). 1H NMR consistent with expected product. Both fractions clean (total 166 mg, 46%).

TLC (5% MeOH/DCM) visualised with UV and vanillin:
TLC 16 hours


NMR:
1H NMR
1H NMR PMY 57-1-A
1H, 13C, 19F NMR PMY 57-1-B


Mass Spec:
HRMS (ESI+) found 357.12285 [M+Na], C17H19N2O4FNa requires 357.12211.

See also:
Synthesis of aryl pyrrole oxazole ester from aldehyde and Serine methyl ester (PMY 46-1)
Synthesis of aryl pyrrole oxazole ester (PMY 45-1)
Hydrolysis of Ethyl 1-(4-fluorophenyl)-2,5-dimethyl-1H-pyrrole-3-carboxylate (JRC 2-1)
Synthesis of pyrrole acid chloride (PMY 32-3)
Coupling of crude PMY 53-2 and pyrrole acid chloride (PMY 55-1)
Synthesis of TCMDC-123812 via acid chloride (PMY 10-6)

Risk and Hazard Assessment:
See: Synthesis of TCMDC-123812 via acid chloride (PMY 10-6)
Linked Posts
Attached Files
Scheme
TLC 16 hours
1H NMR PMY 57-1-A
1H NMR
1H, 13C, 19F NMR PMY 57-1-B