L-Hydroxyproline → (2S,4R)-1-[(9H-fluoren-9-ylmethoxy)carbonyl]-4-hydroxypyrrolidine-2-carboxylic acid

HRID 1046957Notes

Reaction equation

HRID 1046957 reaction equation
[NH:1]1[CH2:9][C@H:7]([OH:8])[CH2:6][C@H:2]1[C:3]([OH:5])=[O:4].C([O-])([O-])=O.[Na+].[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]>C1COCC1.O.C1COCC1.O>[N:1]1([C:16]([O:18][CH2:19][CH:20]2[C:21]3[C:26](=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:27]3[C:32]2=[CH:31][CH:30]=[CH:29][CH:28]=3)=[O:17])[CH2:9][C@H:7]([OH:8])[CH2:6][C@H:2]1[C:3]([OH:5])=[O:4]

Participants

7

Reactant 3

HCID 5810L-HydroxyprolineHCID 10340Sodium CarbonateHCID 134122N-(9-Fluorenylmethoxycarbonyloxy)succinimide

Product 1

HCID 2756109(2S,4R)-1-[(9H-fluoren-9-ylmethoxy)carbonyl]-4-hydroxypyrrolidine-2-carboxylic acid

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 21881883Oxolane--water (1/1)Solvent

Procedure

To a suspension of H-trans-Hyp-OH (122.5 g, 362 mmol) in THF/H2O (100 mL/200 mL) is added 2N Na2CO3 (250 mL), along with addition of a suspension of Fmoc-OSu in THF (700 mL). The mixture is stirred at room temperature overnight. The mixture is diluted with H2O (2700 mL) and extracted with ether/petroleum ether (500 mL/500 mL) The aqueous layer is acidified by 6N HCl and then extracted with ethyl acetate (1×1000 mL, 1×500 mL). The combined extract is washed with brine once and dried over Na2SO4. After removal of most of solvent, the residue is treated with ethyl ether (200 mL). The white solid is filtered and dried under vacuum. Yield: 125.8 g (356 mmol, 98%)

Workup

  1. extractionextracted with ether/petroleum ether (500 mL/500 mL) The aqueous layer
  2. extractionextracted with ethyl acetate (1×1000 mL, 1×500 mL)
  3. extractionThe combined extract
  4. washis washed with brine once
  5. dry with materialdried over Na2SO4
  6. customAfter removal of most of solvent
  7. additionthe residue is treated with ethyl ether (200 mL)
  8. filtrationThe white solid is filtered
  9. customdried under vacuum

Sources & evidence

ORD record
ord-a66caa9f0a7841838ff5dc661b2e53c6
Source dataset
uspto-grants-2013_10
Patent number
US08569452B2

Reaction notes

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