2-Methyl-2-butene → 5-[4-(2-amino-2-oxoethoxy)phenyl]-6-chloro-1H-indole-3-carboxylic acid

HRID 1054735Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1054735
[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:23]=[CH:22][C:16]([O:17][CH2:18][C:19]([NH2:21])=[O:20])=[CH:15][CH:14]=1.CC(=CC)C.Cl([O-])=[O:30].[Na+].O.OP([O-])(O)=O.[Na+]>C(#N)C.C(O)(C)(C)C.O>[NH2:21][C:19](=[O:20])[CH2:18][O:17][C:16]1[CH:15]=[CH:14][C:13]([C:3]2[CH:4]=[C:5]3[C:9](=[CH:10][C:2]=2[Cl:1])[NH:8][CH:7]=[C:6]3[C:11]([OH:30])=[O:12])=[CH:23][CH:22]=1

Komponenten

8

Edukt 4

HCID 105532-Methyl-2-buteneHCID 516949Sodium Phosphate, Monobasic, MonohydrateHCID 23668197Sodium ChloriteHCID 866987342-[4-(6-chloro-3-formyl-1H-indol-5-yl)phenoxy]acetamide

Produkt 1

HCID 866987355-[4-(2-amino-2-oxoethoxy)phenyl]-6-chloro-1H-indole-3-carboxylic acidAusbeute 21,3 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 6342AcetonitrileLösungsmittelHCID 6386tert-ButanolLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

To a mixture of 2-[4-(6-chloro-3-formyl-1H-indol-5-yl)phenoxy]acetamide (100 mg, 0.30 mmol) in acetonitrile (5 mL) and tert-butanol (5 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 (540 mg, 6.00 mmol) and sodium phosphate monobasic hydrate (850 mg, 6.00 mmol) in water (5 mL) dropwise via additional funnel. The ice bath was removed and the reaction was stirred at room temperature for 48 h. The solvent was removed in vacuo to give a residue, which was purified by prep-HPLC (Prep-HPLC: Column: Kromasil Eternity-5-C18 150*30 mm*5 μm Mobile phase: from 24% MeCN in water (0.225% FA) to 34% MeCN in water (0.225% FA); Wavelength: 220 nm Flow rate: 30 mL/min) to give 5-[4-(2-amino-2-oxoethoxy)phenyl]-6-chloro-1H-indole-3-carboxylic acid (22 mg, 20% yield) as a white solid. MS (ES+) 344.8 (M+H)+. 1H NMR (400 MHz, CD3OD) δ 8.01-7.99 (m, 2 H), 7.57 (s, 1 H), 7.43-7.39 (m, 2 H), 7.07-7.05 (m, 2 H), 4.56 (s, 2 H).

Aufarbeitung

  1. customThe ice bath was removed
  2. customThe solvent was removed in vacuo
  3. customto give a residue, which
  4. customwas purified by prep-HPLC (Prep-HPLC: Column: Kromasil Eternity-5-C18 150*30 mm*5 μm Mobile phase: from 24% MeCN in water (0.225% FA) to 34% MeCN in water (0.225% FA); Wavelength: 220 nm Flow rate: 30 mL/min)

Quellen und Nachweise

ORD-Eintrag
ord-b3064bd1da0b4b6d8779e46b47e17cf0
Quelldatensatz
uspto-grants-2016_07
Patentnummer
US09394285B2

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