Exp191-3.gif

Objective

To optimize the reaction from Exp099 to make this Ugi product using Mettler Toledo's automated MiniMapper liquid handler and MiniBlock systems. Forty eight reactions are run in parallel using four reactants (2.0M in methanol) in different solvents / concentration.

Procedure

Make up 2M methanol solutions (25mL each) of starting materials - benzaldehyde (5.077 mL) furfurylamine (4.418mL), boc-glycine (8.759 g) and tert-butyl isocyanide (5.655 mL). The densities and m.w. data was obtained from the Ugi Chemicals table.
The following are added in this order in a reaction tube equipped with a filtration frit
1) The additional solvent
2) The furfurylamine solution
3) The benzaldehyde solution
4) The boc-glycine solution
5) The tert-butyl isocyanide solution
6) The reaction mixture is placed in a shaker for 16 h then filtered
7) Two washed are performed by adding methanol (1 mL) followed by 15 min shaking then filter off
8) Product is dried under high vacuum
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
The yields are listed in this spreadsheet

Discussion


Conclusion

The results of this experiment were combined with Exp201 and Exp203 and reported in detail in Paper03.

Log

Minimapper Log
2008-07-18
16:00 Weighed the filter tubes for the run in a red miniblock
18:53 Minimapper started the run with the Red miniblock (1st priming with methanol, addition of methanol to first 18 slots, then priming with ethanol, addition of ethanol to the next 12 filter tubes, then priming with acetonitrile, addition of CH3CN to the next 12 filter tubes, then priming with THF, addition of THF to the last 6 filter tubes, then priming with methanol again, addition of the first reagent (amine) to all 48 tubes,wash canula with methanol, addition of benzaldehyde to all, wash canula with methanol, addition of boc-glycine to all tubes, wash canula with methanol and then addition of t-butyl isocyanide to all 48 filter tubes...and finally washing the canula with methanol.
20:15 Minimapper completed the addition of solvents and reagents to the miniblock.
20:17 Moved the miniblock on to the shaker set at 410rpm
2008-07-19
17:20 Removed the miniblock from the shaker- performed a parallel filtration to remove solvent.
17:35 Programed the minimapper to deliver methanol (1mL) to each filter tube.
17:50 After the addition of methanol, the miniblock was moved over to the shaker (600rpm)
18:00 Removed from the shaker and did a parallel filtration..
18:10 Added methanol to each filter tube by auto addition with the minimapper.
18:30 After the addition of methanol, the miniblock was moved over to the shaker (600rpm)
18:40 Removed from the shaker and performed a parallel filtration..
18:45 The filter tubes were removed from the miniblock and placed in a desiccator connected to a high vac.
2008-07-20
11:30 Weighed the filter tubes.


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)