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

HRID 440450Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 440450
[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]

Komponenten

6

Edukt 3

HCID 5810L-HydroxyprolineHCID 516892Sodium BicarbonateHCID 14261773Fluorenylmethyl chloroformate

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 1140TolueneLösungsmittelHCID 218864351,4-Dioxane--water (1/1)Lösungsmittel

Versuchsvorschrift

Hydroxyproline, 1, (5.00 g, 38.2 mmol) and NaHCO3 (8.00 g, 95.2 mmol) were suspended in 150 ml H2O/Dioxane (1:1). Fluorenylmethyl chloroformate (11.4 g, 44.0 mmol) in 25 ml 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 50 ml saturated NaHCO3 solution and 50 ml water. The solution was then extracted with 100 ml diethyl ether. The aqueous layer was acidified to pH 1 with concentrated HCl, and extracted twice with ethyl acetate, and the organic extracts washed with brine. The solution was dried with MgSO4, filtered and the solvent removed in vacuo. The pure product crystallized from the concentrated solution. Yield: 13.4 g (100%). 1H NMR: (CDCl3, 200 MHz) δ7.75-7.15 (8H, m, ArH), 4.55-4.05 (5H, m, ArCHCH2, H2, H4), 3.65-3.45 (2H, m, 2 H5), 2.35-2.10 (2H, m, 2 H3).

Aufarbeitung

  1. additionto rise above 25° C. during the addition
  2. customquenched with 50 ml saturated NaHCO3 solution and 50 ml water
  3. extractionThe solution was then extracted with 100 ml diethyl ether
  4. extractionextracted twice with ethyl acetate
  5. washthe organic extracts washed with brine
  6. dry with materialThe solution was dried with MgSO4
  7. filtrationfiltered
  8. customthe solvent removed in vacuo
  9. customThe pure product crystallized from the concentrated solution

Quellen und Nachweise

ORD-Eintrag
ord-d427a4102d664c899dfa4eff67b6c1a1
Quelldatensatz
uspto-grants-1996_05
Patentnummer
US05519134

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