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

HRID 1939857Notes

Reaction equation

HRID 1939857 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+].Cl[C:16]([O:18][CH2:19][C:20]1[C:32]2[CH2:31][C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[C:24]=2[CH:23]=[CH:22][CH:21]=1)=[O:17]>O.O1CCOCC1.C1(C)C=CC=CC=1>[C:16]([N:1]1[CH2:9][C@H:7]([OH:8])[CH2:6][C@H:2]1[C:3]([OH:5])=[O:4])([O:18][CH2:19][CH:20]1[C:21]2[C:28](=[CH:29][CH:24]=[CH:23][CH:22]=2)[C:27]2[C:32]1=[CH:31][CH:30]=[CH:25][CH:26]=2)=[O:17]

Participants

6

Reactant 3

HCID 5810L-HydroxyprolineHCID 516892Sodium BicarbonateHCID 14261773Fluorenylmethyl chloroformate

Product 1

HCID 2756109(2S,4R)-1-[(9H-fluoren-9-ylmethoxy)carbonyl]-4-hydroxypyrrolidine-2-carboxylic acidYield 100%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 218864351,4-Dioxane--water (1/1)Solvent

Procedure

Hydroxyproline (5.0 g, 38.2 mmol) and sodium bicarbonate (8.0 g, 95.2 mmol) were suspended in 150 mL of water:dioxane (1:1). Fluorenylmethyl chloroformate (11.4 g, 44.0 mmol) in 25 mL of toluene was added dropwise. The temperature of the reaction was not allowed to rise above 25° C. during the addition. The mixture was stirred vigorously overnight, and then quenched with saturated sodium bicarbonate (50 mL) and water (50 mL). The solution was then extracted with diethyl ether (100 mL). The aqueous layer was acidified to pH 1 with concentrated HCl and extracted twice with ethyl acetate. The organic extracts were washed with brine. The solution was then dried with anhydrous magnesium sulfate, filtered and the solvent removed in vacuo. After crystallization, 13.4 g (100%) of pure N-Fmoc-trans-4-hydroxy-L-proline was obtained.

Workup

  1. additionto rise above 25° C. during the addition
  2. customquenched with saturated sodium bicarbonate (50 mL) and water (50 mL)
  3. extractionThe solution was then extracted with diethyl ether (100 mL)
  4. extractionextracted twice with ethyl acetate
  5. washThe organic extracts were washed with brine
  6. dry with materialThe solution was then dried with anhydrous magnesium sulfate
  7. filtrationfiltered
  8. customthe solvent removed in vacuo
  9. customAfter crystallization

Sources & evidence

ORD record
ord-06031e28f6e74773a8e79e6de69e6ebd
Source dataset
uspto-grants-1997_12
Patent number
US05698391

Reaction notes

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