1,2-Dichloroethane → 3-Hydroxy-4-{2-[(morpholine-4-carbonyl)-amino]-3-phenylmethanesulfonyl-propionylamino}-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 460405Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 460405
[N:1]1([C:7]([NH:9][CH:10]([CH2:14][S:15]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)(=[O:17])=[O:16])[C:11](O)=[O:12])=[O:8])[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.[C:25]([O:29][C:30]([N:32]1[CH2:36][CH:35]([OH:37])[CH:34]([NH2:38])[CH2:33]1)=[O:31])([CH3:28])([CH3:27])[CH3:26].C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CN1CCOCC1>ClCCl>[C:25]([O:29][C:30]([N:32]1[CH2:33][CH:34]([NH:38][C:11](=[O:12])[CH:10]([NH:9][C:7]([N:1]2[CH2:2][CH2:3][O:4][CH2:5][CH2:6]2)=[O:8])[CH2:14][S:15]([CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)(=[O:17])=[O:16])[CH:35]([OH:37])[CH2:36]1)=[O:31])([CH3:28])([CH3:26])[CH3:27]

Komponenten

7

Edukt 5

HCID 111,2-DichloroethaneHCID 79724-MethylmorpholineHCID 757711-HydroxybenzotriazoleHCID 11229445tert-Butyl 3-amino-4-hydroxypyrrolidine-1-carboxylateHCID 112797342-[(Morpholine-4-carbonyl)-amino]-3-phenylmethanesulfonyl-propionic acid

Produkt 1

HCID 694401533-Hydroxy-4-{2-[(morpholine-4-carbonyl)-amino]-3-phenylmethanesulfonyl-propionylamino}-pyrrolidine-1-carboxylic acid tert-butyl esterAusbeute 69,3 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

2-[(Morpholine-4-carbonyl)-amino]-3-phenylmethanesulfonyl-propionic acid (1 g, 2.8 mmol), 3-amino-4-hydroxy-pyrrolidine-1-carboxylic acid tert-butyl ester (700 mg, 3.46 mmol) prepared as in Reference 1, EDC (1.5 g, 7.8 mmol), and HOBt (1.5 g, 9.6 mmol) were combined. Dichloromethane (10 mL) was added and then 4-methylmorpholine (1.5 mL). The mixture was stirred at ambient temperature for 2 hours. After dilution with ethyl acetate (200 mL) the solution was washed with saturated aqueous NaHCO3 (100 mL) and brine (100 mL), dried with MgSO4 and evaporated under vacuum. 3-Hydroxy-4-{2-[(morpholine-4-carbonyl)-amino]-3-phenylmethanesulfonyl-propionylamino}-pyrrolidine-1-carboxylic acid tert-butyl ester (1.05 g, 1.94 mmol) was obtained as yellowish foam and was dissolved in dichloromethane (6 mL). Trifluoroacetic acid (6 mL) was added and the mixture was stirred at ambient temperature for 1 hour. Evaporation under vacuum gave crude morpholine-4-carboxylic acid [1-(4-hydroxy-pyrrolidin-3-ylcarbamoyl)-2-phenylmethanesulfonyl-ethyl]-amide as TFA salt, which was used without further purification.

Aufarbeitung

  1. washAfter dilution with ethyl acetate (200 mL) the solution was washed with saturated aqueous NaHCO3 (100 mL) and brine (100 mL)
  2. dry with materialdried with MgSO4
  3. customevaporated under vacuum

Quellen und Nachweise

ORD-Eintrag
ord-ca8a734dc5884a048cb832753fd83f02
Quelldatensatz
uspto-grants-2007_03
Patentnummer
US07196099B2

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