2-Methyl-2-butene → 6-chloro-5-{4-[2-(morpholin-4-yl)-2-oxoethyl]phenyl}-1H-indole-3-carboxylic acid

HRID 338409

Reaktionsgleichung

Reaktionsgleichung von HRID 338409
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([CH:11]=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:18]=[CH:17][C:16]([CH2:19][C:20]([N:22]2[CH2:27][CH2:26][O:25][CH2:24][CH2:23]2)=[O:21])=[CH:15][CH:14]=1.CC(=CC)C.Cl([O-])=[O:34].[Na+].O.O.OP([O-])(O)=O.[Na+]>C(#N)C.C(O)(C)(C)C.O>[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]([OH:34])=[O:12])=[CH:7][NH:8]2)=[CH:4][C:3]=1[C:13]1[CH:14]=[CH:15][C:16]([CH2:19][C:20]([N:22]2[CH2:23][CH2:24][O:25][CH2:26][CH2:27]2)=[O:21])=[CH:17][CH:18]=1

Komponenten

8

Edukt 4

HCID 105532-Methyl-2-buteneHCID 23668197Sodium ChloriteHCID 23673460Sodium Phosphate, Monobasic, DihydrateHCID 866987456-chloro-5-{4-[2-(morpholin-4-yl)-2-oxoethyl]phenyl}-1H-indole-3-carbaldehyde

Produkt 1

HCID 866987466-chloro-5-{4-[2-(morpholin-4-yl)-2-oxoethyl]phenyl}-1H-indole-3-carboxylic acidAusbeute 28 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6342AcetonitrileLösungsmittelHCID 6386tert-ButanolLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a solution of 6-chloro-5-{4-[2-(morpholin-4-yl)-2-oxoethyl]phenyl}-1H-indole-3-carbaldehyde (249 mg, 0.650 mmol) in acetonitrile (6 mL) and tert-butanol (6 mL) was added 2-methyl-2-butene (4 mL). The reaction mixture was cooled to 0° C. and treated with a solution of sodium chlorite (880 mg, 13.1 mmol) and sodium phosphate monobasic dihydrate (2030 mg, 13.01 mmol) in water (3 mL) via addition funnel. The icebath was removed and the mixture was allowed to warm to room temperature. The reaction mixture was stirred at room temperature for 18 hours. The reaction was quenched with aqueous sodium sulfite, concentrated in vacuo and extracted with ethyl acetate (4×25 mL). The combined organic phases were washed with brine (20 mL), dried and concentrated in vacuo. The crude product was purified by prep-HPLC (Column: Phenomenex Synergi C18 150*30 mm*4 μm; Mobile phase: from 38% MeCN in water (0.225% FA) to 58% MeCN in water (0.225% FA); Wavelength: 220 nm) to afford the title compound (65 mg, 28% yield) as a white solid. MS (ES+) 399.0 (M+H)+.

Aufarbeitung

  1. customThe icebath was removed
  2. temperatureto warm to room temperature
  3. customThe reaction was quenched with aqueous sodium sulfite
  4. concentrationconcentrated in vacuo
  5. extractionextracted with ethyl acetate (4×25 mL)
  6. washThe combined organic phases were washed with brine (20 mL)
  7. customdried
  8. concentrationconcentrated in vacuo
  9. customThe crude product was purified by prep-HPLC (Column: Phenomenex Synergi C18 150*30 mm*4 μm; Mobile phase: from 38% MeCN in water (0.225% FA) to 58% MeCN in water (0.225% FA); Wavelength: 220 nm)

Quellen und Nachweise

ORD-Eintrag
ord-20ceb14a61494f089bae5669b96774bb
Quelldatensatz
uspto-grants-2014_11
Patentnummer
US08889730B2

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