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.

Procedure

Make up 2M methanol solutions (25mL each) of starting materials - Furfurylamine (4.418mL), Boc-glycine (8.759g) and tert-butyl isocyanide (5.655mL) and 2.077M Benzaldehyde (5.275mL ) in methanol.
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 - 0.5M, 0.25M and 0.1M
reagent excess - 1.0 and 1.2 equivalents
solvent (for 0.25 and 0.1 conc only): ethanol, acetonitrile, THF
Limiting reagent conc : 0.2mmol

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

Map file ;

Results

Job file.

Discussion


Conclusion

The results are not meaningful because the liquid handler was not properly programmed.

Log

Log file1 ;

2008-07-09
10:00 Made-up 2M stock solutions (25mL) of Benzaldehyde, fufurylamine, boc-glycine, and t-butylisocyanide in methanol.
11:00 Weighed empty reaction tubes, weights noted in the spreadsheet.
16:50 Started running the minimapperl; to dispense the solvents and reactants to each reaction tube.
19:30 Minimapper completed additions to the reaction tubes, smoothly.
19:35 Set the miniblock on the shaker at 400 rpm.
2008-07-10
15:30 Removed the miniblock from the shaker and vacuumed off excess solvent.
15:35 Set the miniblock on the minimapper and programmed it to deliver methanol (1mL) to each reaction tube.
15:50 Minimapper completed adding methanol to the reaction tubes.
15:51 Placed the miniblock on the shaker and started shaking at 400 rpm for 15 min.
16:05 Removed from the shaker and vacuumed off the solvent from the reaction tubes.
16:15 Set the miniblock on the minimapper and programmed it to deliver methanol (1mL) to each reaction tube for washing a second time.
16:35 Minimapper completed adding methanol to the reaction tubes.
16:36 Placed the miniblock on the shaker and started shaking at 400 rpm for 15 min.
16:51 Removed from the shaker and vacuumed off the solvent from the reaction tubes. The miniblock is let connected to the house vac for 30min.
17:21 The miniblock is disconnected from the house vac and placed in a desiccator connected to a high-vac.
20:50 Removed from the desiccator and weighed the dry filter tubes...realized that the tubes could still have been wet (weighed more than should have been)
21:20 Placed the miniblock in the desiccator connected to a high vac and left it for overnight drying.
2008-07-11
09:20 Removed from the desiccator and weighed the dry filter tubes...the weights did not differ from the previous days weights.

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)