Dicyclohexylcarbodiimide → N,N'-Dicyclohexylurea

HRID 2238471Notes

Reaction equation

HRID 2238471 reaction equation
[OH:1]N1C(=O)CCC1=O.[CH:9]1([N:15]=[C:16]=[N:17][CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)[CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1.CN(C1C=CC=CN=1)C>C1COCC1>[C:16]([NH:15][CH:9]1[CH2:10][CH2:11][CH2:12][CH2:13][CH2:14]1)([NH:17][CH:18]1[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]1)=[O:1]

Participants

5

Reactant 3

HCID 10868DicyclohexylcarbodiimideHCID 218852-DimethylaminopyridineHCID 80170N-Hydroxysuccinimide

Product 1

HCID 4277N,N'-Dicyclohexylurea

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

N-hydroxysuccinimide (0.534 g, 4.64 mmol) was added to a solution of Gly-1-Me-HOPO (1.220 g, 3.87 mmol) in dry THF (60 ml) under a nitrogen atmosphere. After stirring for 20 min, dicyclohexylcarbodiimide (DCC, 0.956, 4.64 mmol) and dimethylaminopyridine (DMAP, 0.044 g, 0.46 mmol) were added. After 9 h, a white precipitate of dicyclohexylurea (DCU) had formed and the formation of the NHS-activated ester was judged to be complete by TLC. TREN (0.141 g, 0.967 mmol, 0.25equiv.) was added. The solvent was evaporated and the residue taken up in a 1.0M aqueous solution of HCl (50 ml). The suspension was filtered and the filtrate washed with CH2Cl2 (2×50 ml). The combined organic fractions were then back-extracted once with 1.0 M HCl (50 ml). 10M NaOH was added drop-wise to the combined aqueous fractions until the pH reached 11. The aqueous fractions were then extracted with CH2Cl2 (10×50 ml) and EtOAc (3×50 ml). The organic extracts were combined, dried (Na2SO4) and evaporated to dryness. The product was perified by a gradient flash silica column (2-8% CH3OH in CH2Cl2). Evaporation of the solvent afforded a white foam (Yield: 0.753 g, 56%). 1H NMR (CDCl3, 400 MHz): δ=8.58 (t, J=5.4 Hz, 3H, HOPO-glycine NH), 7.27-7.51 (m, 18H, Bn and glycine-TREN NH), 7.00 (d, J=7.2 Hz, 3H, HOPO), 6.59 (d, J=7.2 Hz, 3H, HOPO), 5.42 (s, 6H, Bn CH2), 3.85 (d, J=5.4 Hz, 6H, glycine CH2), 3.51 (s, 9H, N-CH3), 3.20 (m, 6H, TREN NHCH2), 2.51 (m, 6H, TREN NCH2) ppm. Anal. Calcd (Found) for C54H60N10O12.2H2O: C, 60.21 (59.96); H, 5.99 (5.96); N, 13.00 (12.93). FAB-MS (+): m/z: 1041.5 [M+H]+.

Workup

  1. waitAfter 9 h

Sources & evidence

ORD record
ord-c3c5cb62ac174c6b87011d57306bf000
Source dataset
uspto-grants-2010_05
Patent number
US07718781B2

Reaction notes

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