Hydrochloric Acid → N-{[(9H-Fluoren-9-yl)methoxy]carbonyl}-D-glutamic acid

HRID 1526671Notes

Reaction equation

HRID 1526671 reaction equation
[NH2:1][C@@H:2]([C:8]([OH:10])=[O:9])[CH2:3][CH2:4][C:5]([OH:7])=[O:6].C([O-])(O)=O.[Na+].[C:16](ON1C(=O)CCC1=O)([O:18][CH2:19][CH:20]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:26]2[C:21]1=[CH:22][CH:23]=[CH:24][CH:25]=2)=[O:17].Cl>CC(C)=O.O>[NH:1]([C:16]([O:18][CH2:19][CH:20]1[C:21]2[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=2)[C:27]2[C:32]1=[CH:31][CH:30]=[CH:29][CH:28]=2)=[O:17])[C@@H:2]([C:8]([OH:10])=[O:9])[CH2:3][CH2:4][C:5](=[O:7])[OH:6]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 23327D-Glutamic AcidHCID 134122N-(9-Fluorenylmethoxycarbonyloxy)succinimideHCID 516892Sodium Bicarbonate

Product 1

HCID 40501223N-{[(9H-Fluoren-9-yl)methoxy]carbonyl}-D-glutamic acidYield 81%

Reagents, catalysts & solvents 2

HCID 180AcetoneSolventHCID 962WaterSolvent

Procedure

In an ice-water bath, a solution of D-glutamic acid (H-D-Glu-OH, 29.4 g, 1.0 eq) in a mixture of acetone and H2O (V/V=1:1) was stirred. After the solid was fully dissolved, NaHCO3 (23.3 g, 1.1 eq) was added in portions, then Fmoc-OSu (67.4 g, 1.0 eq) were added slowly and the reaction was stirred for additional 3 days at r.t. The mixture was then cooled in ice-water bath again, and pH was adjusted to 2-3 with 2.0N HCl. After removal of acetone under reduced pressure, the remaining solution was extracted with AcOEt (400 mL×4). The organic layer was separated and combined, dried with MgSO4 overnight, and concentrated to a small volume under reduced pressure. Then residue was recrystallized with ethylacetate-cyclohexane system. After filtration, 59.8 g of target product was obtained as a white solid with a yield of 81%.

Workup

  1. dissolutionAfter the solid was fully dissolved
  2. stirringthe reaction was stirred for additional 3 days at r.t
  3. customAfter removal of acetone under reduced pressure
  4. extractionthe remaining solution was extracted with AcOEt (400 mL×4)
  5. customThe organic layer was separated
  6. dry with materialdried with MgSO4 overnight
  7. concentrationconcentrated to a small volume under reduced pressure
  8. customThen residue was recrystallized with ethylacetate-cyclohexane system
  9. filtrationAfter filtration, 59.8 g of target product
  10. customwas obtained as a white solid with a yield of 81%

Sources & evidence

ORD record
ord-559850c548114a2b90c38f30c12561b6
Source dataset
uspto-grants-2015_07
Patent number
US09085605B2

Reaction notes

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