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4th June 2010 @ 08:28
Preparation of the ‘Ugi intermediate’ of (MeO)2-PZQ as starting material for the Pictet-Spengler cyclisation – test reactions

N-(2,2-dimethoxyethyl)-N-(2-((3,4-dimethoxyphenethyl)amino)-2-oxoethyl)cyclohexanecarboxamide

Reaction Scheme


Table1


Hazard and Risk Assessment:
Reaction Class: 2
Hazards: X Irritant, C Corrosive
Risk rating: U = Unlikely

Start time: 4:30 pm 04/06/10
End time: 11:00 am 05/06/2010

Preparation of the starting material MW14-3

To a solution of MW14-3 (50 mg, 153 µmol) and Et3N (23.3 mg, 32µL, 230 µmol) in dry DCM (2 mL) was added of cyclohexanecarboxylic acid chloride (24.7 mg, 23µL, 169 µmol) at 0°C, warmed to room temperature and stirred for 2 h.
- TLC (EA = 100%, stain: ceric ammonium molybdate, Rf = 0.33) still some starting material

TLC1


Stirring for further 12 h at room temperature - no significant change in the consumption of the starting material

Work-up: quenched with water, extracted with DCM, washed with aq. ammonium chloride, dried over sodium sulfate, concentrated.
- crude product: 81 mg yellow liquid

1H NMR: good conversion to MW32, impurities of starting material and/or side products



MW32-2: Testing another base

Reaction Scheme2


Table2


Start time: 6:50 PM 07/06/2010
End time: 10:40 PM 07/06/2010

To a suspension of MW14-3 (50 mg, 153 µmol) and Na2CO3 (24.4 mg, 230 µmol) in dry DCM (2 mL) was added of cyclohexanecarboxylic acid chloride (24.7 mg, 169 µmol) at 0°C and warmed to room temperature.
- after 4 h: TLC (EA 100%, ceric ammonium molybdate) --> slow and unselective reaction, still starting material left
TLC MW32-2


--> upscaling under the conditions of MW32-1: see MW32-3

Analytical data:
-> see MW40-1
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Attached Files
Reaction Scheme
Table1
TLC1
1H NMR MW32-1
Reaction Scheme2
Table2
TLC MW32-2
TLC MW32-2