2-Methyl-2-butene → 4,6-difluoro-5-[4-(3-hydroxyoxetan-3-yl)phenyl]-1H-indole-3-carboxylic acid

HRID 338280Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 338280
[F:1][C:2]1[C:10]([C:11]2[CH:16]=[CH:15][C:14]([C:17]3([OH:21])[CH2:20][O:19][CH2:18]3)=[CH:13][CH:12]=2)=[C:9]([F:22])[CH:8]=[C:7]2[C:3]=1[C:4]([CH:23]=[O:24])=[CH:5][NH:6]2.CC(=CC)C.Cl([O-])=[O:31].[Na+].O.OP([O-])(O)=O.[Na+]>C(#N)C.O.C(O)(C)(C)C>[F:1][C:2]1[C:10]([C:11]2[CH:16]=[CH:15][C:14]([C:17]3([OH:21])[CH2:20][O:19][CH2:18]3)=[CH:13][CH:12]=2)=[C:9]([F:22])[CH:8]=[C:7]2[C:3]=1[C:4]([C:23]([OH:31])=[O:24])=[CH:5][NH:6]2

Komponenten

8

Edukt 4

HCID 105532-Methyl-2-buteneHCID 516949Sodium Phosphate, Monobasic, MonohydrateHCID 23668197Sodium ChloriteHCID 866986254,6-difluoro-5-[4-(3-hydroxyoxetan-3-yl)phenyl]-1H-indole-3-carbaldehyde

Produkt 1

HCID 866986264,6-difluoro-5-[4-(3-hydroxyoxetan-3-yl)phenyl]-1H-indole-3-carboxylic acidAusbeute 10,4 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6342AcetonitrileLösungsmittelHCID 6386tert-ButanolLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

A solution of 4,6-difluoro-5-[4-(3-hydroxyoxetan-3-yl)phenyl]-1H-indole-3-carbaldehyde (38 mg, 0.12 mmol) was dissolved in acetonitrile (1 mL) and warm tert-butanol (0.3 mL). The reaction mixture was treated with 2-methyl-2-butene (0.3 ml), cooled to 0° C., and treated with a solution of sodium chlorite (199 mg, 2.36 mmol) and sodium phosphate monobasic hydrate (332 mg, 2.41 mmol) in water (1 mL) via addition funnel. The ice bath was removed, and the reaction mixture was warmed to room temperature and stirred for 5 hours. The reaction mixture was diluted with water (2 mL) and NH4Cl (2 mL). The product was extracted with EtOAc (3×20 mL). The organic layer was concentrated in vacuo to give the crude product, which was purified using prep-HPLC to give the title compound (4.3 mg). MS (ES+) 346.0 (M+H)+. Retention time: 2.04 min. Column: Waters Atlantis dC18 4.6×50 mm, 5 μm. Modifier: TFA 0.05%. Gradient: 95% H2O/5% MeCN linear to 5% H2O/95% MeCN over 4.0 min, HOLD at 5% H2O/95% MeCN to 5.0 min. Flow: 2.0 mL/min.

Aufarbeitung

  1. customThe ice bath was removed
  2. temperaturethe reaction mixture was warmed to room temperature
  3. additionThe reaction mixture was diluted with water (2 mL) and NH4Cl (2 mL)
  4. extractionThe product was extracted with EtOAc (3×20 mL)
  5. concentrationThe organic layer was concentrated in vacuo
  6. customto give the crude product, which
  7. customwas purified

Quellen und Nachweise

ORD-Eintrag
ord-3a01f040eaae464b913ceb99692a7be2
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08889730B2

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