4-Methylmorpholine → 2-(4-Bromo-benzylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 71728

Reaktionsgleichung

Reaktionsgleichung von HRID 71728
[Br:1][C:2]1[CH:9]=[CH:8][C:5]([CH2:6][NH2:7])=[CH:4][CH:3]=1.[C:10]([N:17]1[CH2:24][CH2:23][CH2:22][C@H:18]1[C:19](O)=[O:20])([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11].CN1CCOCC1.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F>CN(C=O)C>[C:13]([O:12][C:10]([N:17]1[CH2:24][CH2:23][CH2:22][CH:18]1[C:19](=[O:20])[NH:7][CH2:6][C:5]1[CH:8]=[CH:9][C:2]([Br:1])=[CH:3][CH:4]=1)=[O:11])([CH3:16])([CH3:15])[CH3:14]

Komponenten

6

Edukt 4

HCID 79724-MethylmorpholineHCID 775714-BromobenzylamineHCID 850831,2-Pyrrolidinedicarboxylic acid, 1-(1,1-dimethylethyl) ester, (2S)-HCID 9886157Methanaminium, N-((dimethylamino)(3H-1,2,3-triazolo(4,5-b)pyridin-3-yloxy)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)

Produkt 1

HCID 666210072-(4-Bromo-benzylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl esterAusbeute 94,4 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

To a mixture of 4-Bromo-benzylamine (2.00 g), Boc-L-proline (2.01 g), and 4-methylmorpholine (3.26 mL) in DMF (40 mL) was added HATU (3.48 g). Reaction mixture was stirred for 45 minutes, then concentrated, diluted with dichloromethane and washed with 10:1 H2O/saturated sodium bicarbonate solution. The aqueous layer was back-extracted with dichloromethane and the combined organic layers were dried (MgSO4), concentrated and purified by flash column chromatography (silica gel, 50 to 100% ethyl acetate/hexanes) to give 2-(4-Bromo-benzylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (3.38 g): LCMS-ESI+: calc'd for C17H24BrN2NaO3: 405.29 (M+Na+). Found: 405.0 (M+Na+).

Aufarbeitung

  1. customReaction mixture
  2. concentrationconcentrated
  3. additiondiluted with dichloromethane
  4. washwashed with 10:1 H2O/saturated sodium bicarbonate solution
  5. extractionThe aqueous layer was back-extracted with dichloromethane
  6. dry with materialthe combined organic layers were dried (MgSO4)
  7. concentrationconcentrated
  8. custompurified by flash column chromatography (silica gel, 50 to 100% ethyl acetate/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-18ab5c1da8e64039a71b959cb4860f96
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08822430B2

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