Hydrochloric Acid → 5-(6-(4-Fluorobenzylcarbamoyl)-2-phenylquinolin-3-yl)pentanoic acid

HRID 927024

Reaktionsgleichung

Reaktionsgleichung von HRID 927024
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:6]([CH2:18][CH2:19][CH2:20][CH2:21][C:22]([OH:24])=[O:23])=[CH:5]2.C1COCC1.C[Si](C)(C)[N-][Si](C)(C)C.[Li+].[Li]CCCC.[F:45][C:46]1[CH:55]=[CH:54][C:49]([CH2:50][N:51]=[C:52]=[O:53])=[CH:48][CH:47]=1.Cl>C(Cl)Cl>[F:45][C:46]1[CH:47]=[CH:48][C:49]([CH2:50][NH:51][C:52]([C:2]2[CH:3]=[C:4]3[C:9](=[CH:10][CH:11]=2)[N:8]=[C:7]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)[C:6]([CH2:18][CH2:19][CH2:20][CH2:21][C:22]([OH:24])=[O:23])=[CH:5]3)=[O:53])=[CH:54][CH:55]=1

Komponenten

8

Edukt 6

HCID 313Hydrochloric AcidHCID 8028TetrahydrofuranHCID 27333761-Fluoro-4-(isocyanatomethyl)benzeneHCID 2733832Lithium HexamethyldisilazideHCID 679816815-(6-Bromo-2-phenylquinolin-3-yl)pentanoic acidHCID 178418339Butyllithium

Produkt 1

HCID 574100785-(6-(4-Fluorobenzylcarbamoyl)-2-phenylquinolin-3-yl)pentanoic acidAusbeute 24 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A solution of 5-(6-bromo-2-phenylquinolin-3-yl)pentanoic acid (1A, 100 mg, 0.260 mmol) in THF (4.00 mL, 49.3 mmol) in a flame dried vial under an atmosphere of nitrogen gas was treated with lithium hexamethyldisilazide (1M/THF, 780 uL). The reaction mixture stirred at RT for 10 min before it was cooled to −78° C. in an acetone/dry ice bath. A solution of nBuLi (2.5M/hexane, 229.0 uL) was slowly added and the reaction progressed for 5 minutes at −78° C. before addition of 4-fluorobenzyl isocyanate (398 uL, 3.12 mmol). The reaction was stirred at −78° C. for 20 minutes, acidified with 10% HCl to pH 1, and diluted with DCM. The biphasic solution was separated and the aqueous layer was extracted with DCM (3×). The combined organic phase was dried over anhydrous sodium sulfate, concentrated and chromatographed (5-100% EtOAc/hexanes) to provide 2 (28 mg; Yield=24%, LCMS (M+H)=439).

Aufarbeitung

  1. temperaturewas cooled to −78° C. in an acetone/dry ice bath
  2. stirringThe reaction was stirred at −78° C. for 20 minutes
  3. customThe biphasic solution was separated
  4. extractionthe aqueous layer was extracted with DCM (3×)
  5. dry with materialThe combined organic phase was dried over anhydrous sodium sulfate
  6. concentrationconcentrated
  7. customchromatographed (5-100% EtOAc/hexanes)
  8. customto provide 2 (28 mg; Yield=24%, LCMS (M+H)=439)

Quellen und Nachweise

ORD-Eintrag
ord-08c56b41de6d408e886334a0977f10df
Quelldatensatz
uspto-grants-2016_03
Patentnummer
US09290453B2

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