Water → (2R)-2-({[(9H-fluoren-9-yl)methoxy]carbonyl}amino)hexanoic acid

HRID 2372007Notes

Reaction equation

HRID 2372007 reaction equation
[NH2:1][C@@H:2]([C:7]([OH:9])=[O:8])[CH2:3][CH2:4][CH2:5][CH3:6].[C:10](Cl)([O:12][CH2:13][CH:14]1[C:26]2[C:21](=[CH:22][CH:23]=[CH:24][CH:25]=2)[C:20]2[C:15]1=[CH:16][CH:17]=[CH:18][CH:19]=2)=[O:11].O>O1CCOCC1>[NH:1]([C:10]([O:12][CH2:13][CH:14]1[C:15]2[C:20](=[CH:19][CH:18]=[CH:17][CH:16]=2)[C:21]2[C:26]1=[CH:25][CH:24]=[CH:23][CH:22]=2)=[O:11])[C@@H:2]([C:7]([OH:9])=[O:8])[CH2:3][CH2:4][CH2:5][CH3:6]

Participants

5

Reactant 3

HCID 962WaterHCID 343679-Fluorenylmethyl chloroformateHCID 456468Norleucine, D-(-)-

Product 1

HCID 2756111(2R)-2-({[(9H-fluoren-9-yl)methoxy]carbonyl}amino)hexanoic acidYield 34.3%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

D-Nle-OH (1.01 g) was dissolved in 30 ml of 10% NaCO3 and 10 ml of dioxan. While stirring, a solution of Fmoc-Cl (2.0 g) in 10 ml of dioxan was added to the solution. After stirring at room temperature for 2 hours, 400 ml of water was added to the mixture. The reaction mixture was extracted twice with 200 ml of ether to remove by-products. Ice was added to the aqueous phase and the mixture was neutralized with conc. hydrochloric acid. After extracting with ethyl acetate, the extract was washed with water. Crystallization from ether gave 933 mg of Fmoc-D-Nle-OH.

Workup

  1. stirringAfter stirring at room temperature for 2 hours
  2. extractionThe reaction mixture was extracted twice with 200 ml of ether
  3. customto remove by-products
  4. additionIce was added to the aqueous phase
  5. extractionAfter extracting with ethyl acetate
  6. washthe extract was washed with water
  7. customCrystallization from ether

Sources & evidence

ORD record
ord-509c312c713e4c05abf5df24b07cc793
Source dataset
uspto-grants-1992_03
Patent number
US05097013

Reaction notes

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