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6th March 2012 @ 02:09
PS = Pictet-Spengler

START: 07/03/12

Extended reaction time from the previous experiment (KAB8-14). KAB1-6 was run for 26 hours, analogous reaction for the dimethoxy N-benzoyl PZQ analogue, (KAB8-16).


Hazard and Risk Assessment
As for KAB8-15 (here).

Previous Related Experiments
AgOTf catalysed PS reaction to give the dimethoxy N-benzoyl PZQ analogue (KAB8-15)
AgOTf catalysed PS reaction to give the dimethoxy PZQ analogue (KAB1-6)
AgOTf catalysed partial PS reaction to give the N-benzoyl PZQ analogue enamide (KAB17-2)
TfOH catalysed PS* reactions to give the dimethoxy PZQ analogues (KAB8-14 & KAB1-5)
Preparation of the dimethoxy Ugi-intermediate (MNR10-2 and MNR10-3)

Following Experiments

MNR10-2 (310 mg, 0.676 mmol) was dissolved in toluene (33 mL) before the addition of AgOTf (16.8 mg, 0.065 mmol, 10 mol%). The reaction mixture was immediately placed in a pre-heated oil bath at 90 °C and refluxed from 10:45. The reaction progress was monitored by TLC against the MNR10-2 starting material and the expected product (identical to KAB8-4).

Monitoring the Reaction Progress by TLC
All TLCs were eluted with EtOAc/hexane, 5:3, v/v and stained with KMnO4. The time noted is from the addition of the AgOTf.
TLC of reaction (6.5 h)
TLC of reaction mixture (26 h)

Workup Procedure
After 26 hours, the reaction mixture was removed from the oil bath and allowed to cool. The mixture was diluted with EtOAc (50 mL), transferred to a separating funnel then washed with citric acid solution (0.5 M, 50 mL). The organic layer was separated and the acidic aqueous layer was basified using sodium hydroxide solution (2 M). After the aqueous layer was extracted with EtOAc (3 × 50 mL), the organic layers were combined, dried over magnesium sulfate, filtered, then concentrated under reduced pressure to give crude KAB8-16 (326 mg, 132%).
TLC of crude KAB8-16

Purified by silica gel column chromatography. Eluent: neat EtOAc. Combined fractions 6-17. Fractions 2-3 contained enamide intermediate. Fractions 4-5 co-spotted.

Summary and Conclusion

NOTES 08/03/12
- Flask weight: 59.4356 g
- Dark solid in crude product. May be silver.

NOTES 12/03/12
- Crude TLC shows mostly product but some enamide intermediate. Planning on purifying by silica gel column chromatography on Wednesday (14/03/12).
Linked Posts
Attached Files
Scheme KAB8-16
Table KAB8-16
TLC of reaction (6.5 h)
TLC of reaction mixture (26 h)
TLC of crude KAB8-16