Exp196

=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. //**Were these made up fresh or used from a previous experiment?**// 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

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
 * Parameters to modify:**

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=
 * 1) Taking the average of 6 runs in a given solvent and concentration we obtain:
 * 2) 0.2M acetonitrile/methanol 60/40: 49.2%
 * 3) 0.2M ethanol/methanol 60/40 42.3%
 * 4) 0.4M methanol 33.0%
 * 5) 0.2M methanol 30.5%
 * 6) 0.2M THF/methanol 60/40 15.1%
 * 7) 0.07M ethanol/methanol 87/13 10.8%
 * 8) 0.07M acetonitrile/methanol 87/13 7.2%
 * 9) 0.07M methanol 0.1%
 * 10) In most cases the excess of isonitrile gave the best result within each solvent/concentration set.

=Conclusion= The results are not meaningful because the liquid handler was not properly programmed. In this case it appears that the line was not flushed sufficiently when changing solvents.

Log
[|Log file1] ;

10:00 Weighed each empty reaction tube (wts in the spreadsheet) 11:00 Made-up 2M (25mL) solutions of the starting materials) 13:04 The minimapper started working on the addition of solvents and chemicals for this run. 14:13 Minimapper completed the run 14:23 Placed the miniblock on the shaker and started shaking at 400rpm. 10:25 Removed the miniblock from the shaker and vacuumed off excess solvent. 10:35 Set the miniblock on the minimapper and programmed it to deliver methanol (1mL) to each reaction tube. 10:50 Minimapper completed adding methanol to the reaction tubes. 10:55 Placed the miniblock on the shaker and started shaking at 400 rpm for 15 min. 11:10 Removed from the shaker and vacuumed off the solvent from the reaction tubes. 11:20 Set the miniblock on the minimapper and programmed it to deliver methanol (1mL) to each reaction tube for washing a second time. 11:55 Minimapper completed adding methanol to the reaction tubes. 12:30 Placed the miniblock on the shaker and started shaking at 400 rpm for 15 min. 12:50 Removed from the shaker and vacuumed off the solvent from the reaction tubes. The miniblock is let connected to the house vac for 30min. 13:25 The miniblock was disconnected from the house vac and placed in a desiccator connected to a high-vac. 16:05 Removed the miniblock from desiccator and weighed the filter tubes...the weights of the tubes/products were recorded into the spreadsheet. =Tags= 
 * 2008-07-10**
 * 2008-07-11**
 * 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)] ||