Hydrochloric Acid → 2-(4'-Bromo-biphenyl-4-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 71854

Reaktionsgleichung

Reaktionsgleichung von HRID 71854
C(O[C:6](=[O:21])[NH:7][C:8]1[CH:13]=[CH:12][C:11]([C:14]2[CH:19]=[CH:18][C:17]([Br:20])=[CH:16][CH:15]=2)=[CH:10][CH:9]=1)(C)(C)C.Cl.[N:23]1([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:30][CH2:29][CH2:28][C@H:24]1C(O)=O.CN(C(ON1N=NC2C=CC=NC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.CCN(C(C)C)C(C)C>CO.CN(C=O)C.C(OCC)(=O)C>[C:34]([O:33][C:31]([N:23]1[CH2:30][CH2:29][CH2:28][CH:24]1[C:6](=[O:21])[NH:7][C:8]1[CH:9]=[CH:10][C:11]([C:14]2[CH:15]=[CH:16][C:17]([Br:20])=[CH:18][CH:19]=2)=[CH:12][CH:13]=1)=[O:32])([CH3:37])([CH3:35])[CH3:36]

Komponenten

9

Edukt 5

HCID 313Hydrochloric AcidHCID 81531DiisopropylethylamineHCID 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)HCID 596105344-Bromo-4'-t-butoxycarbonylaminobiphenyl

Produkt 1

HCID 666213242-(4'-Bromo-biphenyl-4-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl esterAusbeute 95,2 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittelHCID 6228DimethylformamideLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Reaktionsbedingungen

Temperatur
60 °C

Versuchsvorschrift

(4′-Bromo-biphenyl-4-yl)-carbamic acid tert-butyl ester (407 mg, 1.17 mmol) was dissolved in methanol (10 mL) and concentrated HCl (2 mL) was added. The solution was stirred at 60° C. for 1 hour then concentrated. The crude residue was treated with Boc-Pro-OH (302 mg, 1.40 mmol) and HATU (578 mg, 1.52 mmol) and suspended in DMF (6 mL). DIPEA (1.02 mL, 5.85 mmol) was added and the reaction mixture was stirred at RT for 4 hours after which it was diluted with ethyl acetate (200 mL) and washed with water and brine. The organic phase was dried over magnesium sulfate and concentrated. The residue was purified by silica column chromatography (30% to 55% EtOAc/hexanes) to afford 2-(4′-Bromo-biphenyl-4-ylcarbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (496 mg, 95% over 2 steps).

Aufarbeitung

  1. concentrationthen concentrated
  2. stirringthe reaction mixture was stirred at RT for 4 hours after which it
  3. washwashed with water and brine
  4. dry with materialThe organic phase was dried over magnesium sulfate
  5. concentrationconcentrated
  6. customThe residue was purified by silica column chromatography (30% to 55% EtOAc/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-dd81dafd00634a3ba3e3b2423110c4c3
Quelldatensatz
uspto-grants-2014_09
Patentnummer
US08822430B2

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