Exp191-3.gif

Objective

To optimize the reaction from Exp099 to make this Ugi product using Mettler Toledo's automated Minimapper. Forty eight reactions are run in parallel using four reactant (2.0M in methanol) in different solvents / concentration. This run was verified by Tom Osborne.

Procedure

Make up 2M methanol solutions (25mL each) of starting materials - Benzaldehyde (5.077mL ) Furfurylamine (4.418mL), Boc-glycine (8.759g) and tert-butyl isocyanide (5.655mL).
The following are added in this order in a reaction tube equipped with a filtration frit
1) The additional solvent (200uL methanol)
2) The benzaldehyde solution
3) The Furfurylamine solution
4) The Boc-Glycine solution
5) The tert-butyl isocycanide solution

Parameters to modify:
concentration - 0.07M, 0.2M and 0.4M
reagent excess - 1.0 and 1.2 equivalents
solvent (for 0.2 and 0.71 conc only): ethanol, acetonitrile, THF

This is 48 experiments total and they are listed in this spreadsheet

map file

Results

job file
Yields listed in this spreadsheet

Discussion

Averaging over the 6 tubes for a given solvent/concentration, methanol 0.4M, methanol 0.2M, ethanol/methanol 60/40 0.2M and acetonitrile/methanol 60/40 0.2M give the best yields, while the lower concentration 0.07M for all solvents and THF/methanol 60/40 0.2M give the lower yields.

Conclusion

The results of this experiment will have to be verified to confirm there reproducibility.

Log

Log
2008-07-12
08:00 Made-up 2M solution of the starting materials in methanol.
11:20 Started the optimization run on Mettler Toledo's Minimapper. (Using Blue miniblock)
12:47 Minimapper completed liquid handling.
12:48 Removed the miniblock from the minimapper and placed it on the shaker (410rpm)
2008-07-13
12:48 Shaker was turned off and the miniblock was removed from it.
12:50 Drained / Vacuumed off solvent from the filter tubes by performing a parallel filtration
13:00 Programmed the mini mapper to perform 1mL addition of methanol to each filter tube on the miniblock
13:25 Once addition of methanol was completed the miniblock was replaced on the shaker (600rpm)
13:40 Removed the miniblock from the shaker and drained/vacuumed off the solvent.
13:55 Programmed the mini mapper to perform 1mL addition of methanol to each filter tube on the miniblock for the second methanol wash
14:20 Once addition of methanol was completed the miniblock was replaced on the shaker (600rpm)
14:35 Removed the miniblock from the shaker and drained/vacuumed off the solvent, left the miniblock connected to the vacuum line.
15:15 The miniblock was removed from the vacuum line and placed in desiccator connected to high-vac.

Tags


Compound
Inchi Key
Inchi
Furfurylamine
DDRPCXLAQZKBJP-UHFFFAOYAX
InChI=1/C5H7NO/c6-4-5-2-1-3-7-5/h1-3H,4,6H2
Benzaldehyde
HUMNYLRZRPPJDN-UHFFFAOYAE
InChI=1/C7H6O/c8-6-7-4-2-1-3-5-7/h1-6H
tert-butylisocynide
FAGLEPBREOXSAC-UHFFFAOYAL
InChI=1/C5H9N/c1-5(2,3)6-4/h1-3H3
Boc-Glycine
VRPJIFMKZZEXLR-UHFFFAOYAN
InChI=1/C7H13NO4/c1-7(2,3)12-6(11)8-4-5(9)10/h4H2,1-3H3,(H,8,11)(​H,9,10)
Ugi Product
BXAOUWIVXLQYOZ-UHFFFAOYAZ
InChI=1/C24H33N3O5/c1-23(2,3)26-21(29)20(17-11-8-7-9-12-17)27(16- ​18-13-10-14-31-18)19(28)15-25-22(30)32-24(4,5)6/h7-14,20H,15-16H2​ ,1-6H3,(H,25,30)(H,26,29)