1-Ethyl-3-(3'-dimethylaminopropyl)carbodiimide → [(R)-2-((R)-3-fluoro-pyrrolidin-1-yl)-1-methyl-2-oxo-ethyl]-carbamic acid tert-butyl ester

HRID 246093Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 246093
[C:1]([O:5][C:6]([NH:8][C@H:9]([CH3:13])[C:10]([OH:12])=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].CN(C)CCCN=C=NCC.OC1C2N=NNC=2C=CC=1.Cl.[F:36][C@@H:37]1[CH2:41][CH2:40][NH:39][CH2:38]1.C(N(CC)C(C)C)(C)C>CN(C=O)C.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][C@H:9]([CH3:13])[C:10]([N:39]1[CH2:40][CH2:41][C@@H:37]([F:36])[CH2:38]1)=[O:12])([CH3:2])([CH3:3])[CH3:4]

Komponenten

8

Edukt 5

HCID 159081-Ethyl-3-(3'-dimethylaminopropyl)carbodiimideHCID 81531DiisopropylethylamineHCID 637606BOC-D-alanineHCID 2759162(3R)-3-fluoropyrrolidine hydrochlorideHCID 178418300HCID 178418300, Verbindung

Produkt 1

HCID 71280476[(R)-2-((R)-3-fluoro-pyrrolidin-1-yl)-1-methyl-2-oxo-ethyl]-carbamic acid tert-butyl esterAusbeute 94,2 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

(R)-2-tert-Butoxycarbonylamino-propionic acid (1.0 g, 5.3 mmol), 1-(3-(dimethylamino)-propyl)-3-ethylcarbodiimide (2.33 g, 12.2 mmol) and hydroxybenzotriazole (1.64 g, 12.2 mmol) were dissolved in DMF (50 ml). (R)-3-Fluoropyrrolidine hydrochloride (1.66 g, 13.2 mmol) and N,N-diisopropylethylamine (2.95 ml, 16.9 mmol) were added and the mixture was stirred at room temperature for 16 h. Ethyl acetate was added and the solution was washed with 10% citric acid solution three times. The organic layer was washed with sodium bicarbonate solution which was then back-extracted with ethyl acetate four times. The combined organic layers were then washed further with lithium chloride solution, sodium chloride solution, and dried over magnesium sulfate. Concentration of the solution gave 1.3 g (94%) of [(R)-2-((R)-3-fluoro-pyrrolidin-1-yl)-1-methyl-2-oxo-ethyl]-carbamic acid tert-butyl ester.

Aufarbeitung

  1. washthe solution was washed with 10% citric acid solution three times
  2. washThe organic layer was washed with sodium bicarbonate solution which
  3. extractionwas then back-extracted with ethyl acetate four times
  4. washThe combined organic layers were then washed further with lithium chloride solution, sodium chloride solution
  5. dry with materialdried over magnesium sulfate

Quellen und Nachweise

ORD-Eintrag
ord-03cf4a5dffa14522a3df4d493fad2b55
Quelldatensatz
uspto-grants-2014_02
Patentnummer
US08658646B2

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