4-Methylmorpholine → N-[[trans 3-(acetylthiomethyl)-2-oxo-1-aza-cyclodecan-10-yl]-carbonyl]-trans 4-hydroxy-L-proline ethyl ester

HRID 5403

Reaktionsgleichung

Reaktionsgleichung von HRID 5403
[C:1]([S:4][CH2:5][C@H:6]1[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10][C@H:9]([C:16]([OH:18])=O)[NH:8][C:7]1=[O:19])(=[O:3])[CH3:2].ON1C2C=CC=CC=2N=N1.CN1CCOCC1.Cl.[CH2:38]([O:40][C:41](=[O:48])[C@@H:42]1[CH2:46][C@@H:45]([OH:47])[CH2:44][NH:43]1)[CH3:39].Cl.CN(CCCN=C=NCC)C>C(Cl)Cl>[CH2:38]([O:40][C:41](=[O:48])[C@@H:42]1[CH2:46][C@@H:45]([OH:47])[CH2:44][N:43]1[C:16]([C@@H:9]1[NH:8][C:7](=[O:19])[C@@H:6]([CH2:5][S:4][C:1](=[O:3])[CH3:2])[CH2:15][CH2:14][CH2:13][CH2:12][CH2:11][CH2:10]1)=[O:18])[CH3:39]

Komponenten

7

Edukt 5

HCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 12709304Ethyl trans-4-hydroxy-L-prolinate hydrochlorideHCID 86747202trans 3-(Acetylthiomethyl)-2-oxo-1-azacyclodecane-10-carboxylic acid

Produkt 1

HCID 86747211N-[[trans 3-(acetylthiomethyl)-2-oxo-1-aza-cyclodecan-10-yl]-carbonyl]-trans 4-hydroxy-L-proline ethyl ester

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel2×

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

The enantiomer of trans 3-(acetylthiomethyl)-2-oxo-1-azacyclodecane-10-carboxylic acid of Example 16(0.23 g, 0.80 mmol), 1-hydroxybenzotriazole (0.11 g, 0.80 mmol), 4-methylmorpholine (0.22 mL, 2.0 mmol), and L-hydroxyproline ethyl ester hydrochloride (0.16 g, 0.80 mmol) are dissolved in methylene chloride (5.0 mL), and the reaction is cooled to 0° C. To this solution is added N-[dimethylaminopropyl]-N'-ethylcarbodiimide hydrochloride (0.31 g, 1.60 mmol), and the reaction is allowed to warm up to room temperature and stirred overnight. The reaction is diluted with more methylene chloride, and the organic layer is washed with 1N hydrochloric acid, saturated sodium bicarbonate, dried (MgSO4), and the solvent is evaporated. The product is purified by silica gel chromatography (80% ethyl acetate/hexane) to give N-[[trans 3-(acetylthiomethyl)-2-oxo-1-aza-cyclodecan-10-yl]-carbonyl]-trans 4-hydroxy-L-proline ethyl ester as a single enantiomer, [α]D +5.73° (c=4.1 mg/ml, CH2Cl2) which is assigned the 3R, 10S configuration.

Aufarbeitung

  1. temperatureto warm up to room temperature
  2. washthe organic layer is washed with 1N hydrochloric acid, saturated sodium bicarbonate
  3. dry with materialdried (MgSO4)
  4. customthe solvent is evaporated
  5. customThe product is purified by silica gel chromatography (80% ethyl acetate/hexane)

Quellen und Nachweise

ORD-Eintrag
ord-cd1d5c5dc1cf4e4bb0fa6676330d839a
Quelldatensatz
uspto-grants-1993_09
Patentnummer
US05244889

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