To synthesize an amide of Boc Glycine and 5-methylfurfurylamine using DCC, a coupling reagent in chloroform-d.The product amide will serve as a model to understand the reactivity of the furan amide in TFA.


A clean NMR tube was charged with Boc-Gly-OH(175 mg, 1 mmol), CDCl3 (1 mL / 0.03% v/v TMS), 5-methylfurfurylamine (111 uL, 1 mmol), and 4-dimethylaminopyridine (97.6 mg, 0.8 mmol). Then N,N'-dicyclohexylcarbodiimide (206.6 mg,1.1 mmol) was added (see log below while procedure is rewritten)
Characteriation of the product
H NMR -tbutyl -1.42 ppm (9H); CH3 - 2.23 ppm (3H); CH2 3.8 ppm (2H); CH2- 4.35 ppm (2H); furan ring H - 5.86 ppm (1H) and 6.08 ppm (1H); NH- 5.65 ppm (1H) and 7.05 ppm (1H); yield 48%.



5-Methyl furfuryl amine

88A BocGlycine+MFA (H NMR)
t = 02 min
t = 07 min

88B (BocGlycine +MFA + DMAP)

88C (7 mins after DMAP) (BocGlycine +MFA+DMAP+DCC)

88D (5.5 hours and after filtering)

88E (after acid and base wash)

TLC (10:1 Hexanes-Methylene Chloride)
TLC (2:1 Hexanes-Methylene Chloride)
TLC (1:10 Hexanes-Methylene Chloride)

H NMR 500 MHz
H NMR 300 MHz


  1. Estimate the % conversion to the amide after 7 minutes and 5.5 hours.
  2. A pair of doublets at 8.16 (J-6.35 Hz) and 6.48 ppm (J-6.83 Hz) show up in 88D, 5.5 hours after the addition of DCC. These are reminiscent of the pair seen in the disappearing methyl situation. There is no trace of these peaks after 7 minutes or after the work-up. This underscores the importance of monitoring reactions by NMR.
  3. The amide product 88F (the product that will be obtained after filtering 88E) is contaminated by some dicyclohexylurea but should be suitable to treat with 50% TFA in CDCl3 to test for the disappearance of the methyl and furan rings.
  4. Amide assignments.


An amide was successfully synthesized.



05:50 Weighed Boc-Gly-OH(175 mg, 1 mmol), in an nmr tube. Also weighed out 4-dimethylaminopyridine (97.6 mg, 0.8 mmol), N,N'-dicyclohexylcarbodiimide (206.6 mg,1.1 mmol) and placed them in a vacuum dessicator.


09:20 Added CDCl3 (1 mL) to the NMR tube containing Boc-Glycine and obtained H NMR.
09:49 Added MFA (111 uL) to the Boc-Glycine CDCl3 solution in the NMR to obtained 88A. The NMR tube got warm as the amine was added to the amino acid.
09:51 Obtained H NMR of 88A (t = 02 min)
09:56 Obtained H NMR of 88A (t = 07 min)
10:51 Added DMAP to 88A to form 88B.
10:55 Obtained H NMR of 88B
11:13 Completed addition of DCC to the NMR tube, obtained 88C.
11:20 Obtained H NMR of 88C
11:25 Solid has started to appear in the NMR tube, seems to have overwhelmed the NMR tube.... you should still try to get an NMR without filtering
14:30 Transferred the contents of the NMR tube to a centrifuge tube and rinsed the remnaing contents from the NMR tube with 1 mL CDCl3 to obtain 88D
16:54 Obtained H NMR of the clear solution 88D (only 1 mL was used)
17:05 The solution from the NMR tube was combined with the previous solution 88D, in a centrifuge tube.
17:20 The solution (88D) was then washed with 0.5 N HCl (2 mL), after squirting the solution to facilitate good mixing, the bottom organic layer (after separation) was pipetted out. This organic layer was then washed with saturated sodium bicarbonate solution (2 mL) to remove any traces of HCl. The organic layer was again pipetted out and dried over anhydrous magnesium sulfate (1 g).
18:20 The solid MgSO4 was centrifuged, the organic solution was pipetted out into another centrifuge tube. The solid MgSO4 was rinsed out with CDCl3 (1 mL), centrifuged again, and the clear organic layer was combined with the previously collected organic solution.
18:50 The organic solution collected was once again centrifuged to remove any traces of magnesium sulfate solid. The obtained supernatant was transferred into a clean, dry preweighed round bottom flask.
19:10 The solution was set on a rotovap (room temp).
19:30 The round bottom flask was removed from the rotovap and set on a high vac, to achieve complete dryness,
20:00 The round bottom flask was removed from high vac and the precipitate like sludge was weighed to 239 mg.
20:15 The round bottom flask was rinsed with 200 uL of CDCl3 (4 times) and the solution was transferred to a clean NMR tube, however a small layer of the precipitate N,N' dicyclohexylurea appeared floating on CDCl3.-88E
20:25 Apparently the whole procedure of removing urea derviative has tobe performed over again. (Wish I'd used the polymer bound carbodiimide which could have been easily filtered / centrifuged off).
20:58 However an H NMR of 88E was obtained by adding another 400 uL of CDCl3 to the NMR tube so that the solid precipitate remained floating on clear solution.


15:10 Filtered off the solid precipitate from 88E .
15:45 Set the obtained clear liquid on a high vac. Preciepitate still present, dissolved in CDCl3, filtered again, and vacuumed off the solvent.
19:12 Obtained 88F (164 mg); still solid particles visible.
22:00 Filtered 88F again through a sintered glass funnel and collected a clear solution. Everything depends on the amounts of solvent used - you didn't specify but presumably it is more than one ml. The DCurea has a finite solubility in CDCl3 - if you use 2 ml of CDCl3 then filter and evaporate, you will have solid DCU that does not go into one ml of CDCl3. For our purposes, I think it is still worth taking half the material and putting it in 50% TFA/CDCl3 to see if anything happens - make another experiment for this. Just quantify the amount of DCU as a known impurity. By the way, unless you are about to take an NMR use methylene chloride instead of CDCl3
22:30 Set the solution on high vac.


10:30 Removed from the high vac and obtained 88G (121 mg)
12:00 Dissolved the yellow oily liquid in 750 uL of CDCl3 (150 uL x 5) and transferred it to a NMR tube.
15:13 Obtained H NMR of 88G

1.Organic Syntheses, Coll. Vol. 7, p.93 (1990); Vol. 63, p.183 (1985).
2. Suppression of Formation of N,N'-Dicyclohexylurea Derivatives During DCC-Activation of Proline-Containing Dipeptides;Monatshefte für Chemie / Chemical Monthly


Amide: InChI=1/C13H20N2O4/c1-9-5-6-10(18-9)7-14-11(16)8-15-12(17) 19-13(2,3)4/h5-6H,7-8H2,1-4H3,(H,14,16)(H,15,17)
Boc-Gly-OH InChI=1/C7H13NO4/c1-7(2,3)12-6(11)8-4-5(9)10/h4H2,1-3H3,(H,8,11)(H,9,10)
5-methylfurfurylamine InChI=1/C6H9NO/c1-5-2-3-6(4-7)8-5/h2-3H,4,7H2,1H3
DMAP InChI=1/C7H10N2/c1-9(2)7-3-5-8-6-4-7/h3-6H,1-2H3
N,N'-dicyclohexylcarbodiimide InChI=1/C13H22N2/c1-3-7-12(8-4-1)14-11-15-13-9-5-2-6-10-13/h12-13H,1-10H2