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25th June 2012 @ 01:31
Target synthesised in 56% yield.

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Coupling of glycolamide and PMY 44-1 via the acid chloride. Using the method used for PMY 10- and PMY 11- etc.

PMY50-1.png

Reaction Start Time: 10.35 25/06/12

PMY 44-1 (200 mg, 1.0 mmol, 1 equiv.) was stirred in toluene (2 mL). Thionyl chloride (0.15 mL, 2.1 mmol, 2.1 equiv.) was added and the reaction heated to room temperature (lab air temp 14-15 °C). Reaction is a slurry. After 3 hours, reaction is still a slurry. A drop of DMF was added and the reaction heated to reflux. After 1.5 hours the reaction was cooled and concentrated under reduced pressure. The resulting solid was dissolved in THF (4 mL).

Glycolamide (82 mg, 1.1 mmol, 1.1 equiv.), 4-DMAP (48 mg, 0.4 mmol, 0.4 equiv.), DIPEA (350 μL, 2.0 mmol, 2.0 equiv.) were stirred in THF (4 mL) at room temperature. The solution of acid chloride was added dropwise. A precipitate forms immediately. After 20-30 minutes the reaction contained a solid lump of white precipitate, after a further hour the precipitate had redissolved. Reaction stirred overnight. The reaction was concentrated under reduced pressure to an orange gum. Chromatography on silica (40-80% EtOAc/hexane) gave a white solid (143 mg, 56%). 1H NMR consistent with expected product, with traces of solvents.

Mpt. 153-155 °C.

TLC (66% EtOAc/hexane) visualised with UV and vanillin:
TLC prod vs SM
TLC column
TLC overnight


Mass Spec:
Mass Spec

Consistent with product: ESI+ 283.3 [M+Na]
HRMS (ESI+) found 282.08456 [M+Na], C13H13N3O3Na requires 282.08491.

NMR:
1H NMR
1H, 13C NMR

Note: 300 MHz 13C NMR data has an artifact at 74.00 ppm due to filter. Intermittent problem on our machine. See PMY 52-2-A for another example of filter issue. Awaiting fix.

See Also:
Hydrolysis of ethyl 5-methyl-1-phenyl-1H-pyrazole-4-carboxylate (PMY 44-1)

Risk and Hazard Assessment:
See: Synthesis of TCMDC-123794 via acid chloride (PMY 11-2)
Linked Posts
Attached Files
Scheme
TLC overnight
TLC column
TLC prod vs SM
1H NMR
Mass Spec
1H, 13C NMR