Dicyclohexylcarbodiimide → N-(N-Fmoc-6-aminocaproyl)-D-threoninol

HRID 1726357Notes

Reaction equation

HRID 1726357 reaction equation
[C:1]([NH:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][C:24]([OH:26])=O)([O:3][CH2:4][CH:5]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]2[C:6]1=[CH:7][CH:8]=[CH:9][CH:10]=2)=[O:2].ON1C(=O)CCC1=O.C1(N=C=NC2CCCCC2)CCCCC1.[NH2:50][C@@H:51]([CH2:55][OH:56])[C@H:52]([CH3:54])[OH:53]>CN(C=O)C.C(OCC)(=O)C>[C:1]([NH:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][C:24]([NH:50][C@@H:51]([CH2:55][OH:56])[C@H:52]([CH3:54])[OH:53])=[O:26])([O:3][CH2:4][CH:5]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]2[C:6]1=[CH:7][CH:8]=[CH:9][CH:10]=2)=[O:2]

Participants

7

Reactant 4

HCID 10868DicyclohexylcarbodiimideHCID 80170N-HydroxysuccinimideHCID 27560876-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)hexanoic acidHCID 7020320(2S,3S)-2-Amino-1,3-butanediol

Product 1

HCID 21053930N-(N-Fmoc-6-aminocaproyl)-D-threoninol

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
23 °C

Procedure

N-Fmoc-6-aminocaproic acid (10 g, 28.30 mmol) was dissolved in DMF (50 ml) and N-hydroxysuccinimide (3.26 g, 28.30 mmol) and 1,3-dicyclohexylcarbodiimide (5.84 g, 28.3 mmol) were added to the solution. The reaction mixture was stirred at RT (about 23° C.) overnight and the precipitated 1,3-dicyclohexylurea filtered off. To the filtrate D-threoninol (2.98 g, 28.30 mmol) was added and the reaction mixture stirred at RT overnight. The solution was reduced to ca half the volume in vacuo, the residue diluted with about m ml of ethyl acetate and extracted with about x ml of 5% NaHCO3, followed by washing with brine. The organic layer was dried (Na2SO4), evaporated to a syrup and chromatographed by silica gel column chromatography using 1-10% gradient of methanol in ethyl acetate. Fractions containing the product were pooled and evaporated to a white solid (9.94 g, 80%). 1H-NMR (DMSO-d6-D2O) 7.97-7.30 (m, 8H, aromatic), 4.34 (d, J=6.80, 2H, Fm), 4.26 (t, J=6.80, 1H, Fm), 3.9 (m, 1H, H3 Thr), 3.69 (m, 1H, H2 Thr), 3.49 (dd, J=10.6, J=7.0, 1H, H1 Thr), 3.35 (dd, J=10.6, J=6.2, 1H, H1′ Thr), 3.01 (m, 2H, CH2CO Acp), 2.17 (m, 2H, CH2NH Acp), 1.54 (m, 2H, CH2 Acp), 1.45 (m, 2H, CH2 Acp), 1.27 (m, 2H, CH2 Acp), 1.04 (d, J=6.4, 3H, CH3). MS/ESI+ m/z 441.0 (M+H)+.

Workup

  1. filtrationthe precipitated 1,3-dicyclohexylurea filtered off
  2. stirringthe reaction mixture stirred at RT overnight
  3. extractionextracted with about x ml of 5% NaHCO3
  4. washby washing with brine
  5. dry with materialThe organic layer was dried (Na2SO4)
  6. customevaporated to a syrup
  7. customchromatographed by silica gel column chromatography
  8. additionFractions containing the product
  9. customevaporated to a white solid (9.94 g, 80%)

Sources & evidence

ORD record
ord-02f94d8f73e544bfb8218fa8c950fb55
Source dataset
uspto-grants-2009_02
Patent number
US07491805B2

Reaction notes

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