Hydrogen Bromide → 4-Bromo-5-chloro-2-methyl-indole-1-carboxylic acid methyl ester

HRID 1161885

Reaktionsgleichung

Reaktionsgleichung von HRID 1161885
[CH3:1][O:2][C:3]([N:5]1[C:13]2[C:8](=[C:9](N)[C:10]([Cl:14])=[CH:11][CH:12]=2)[CH:7]=[C:6]1[CH3:16])=[O:4].[BrH:17].N([O-])=O.[Na+]>O.Br.O.[Cu]Br>[CH3:1][O:2][C:3]([N:5]1[C:13]2[C:8](=[C:9]([Br:17])[C:10]([Cl:14])=[CH:11][CH:12]=2)[CH:7]=[C:6]1[CH3:16])=[O:4]

Komponenten

7

Edukt 3

HCID 260Hydrogen BromideHCID 23668193Sodium NitriteHCID 668199574-Amino-5-chloro-2-methyl-indole-1-carboxylic acid methyl ester

Produkt 1

HCID 668201134-Bromo-5-chloro-2-methyl-indole-1-carboxylic acid methyl ester

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 24593copper(I) bromideKatalysatorHCID 962WaterLösungsmittel2×HCID 22326455Hydrobromide monohydrateLösungsmittel

Reaktionsbedingungen

Temperatur
0 °C

Versuchsvorschrift

4-Amino-5-chloro-2-methyl-indole-1-carboxylic acid methyl ester (2.04 g, 8.54 mmol) is suspended in a 4.8% solution of HBr in water (75 ml). After cooling to 0° C., a solution of sodium nitrite (1.23 g, 17.94 mmol) in water (30 ml) is slowly added during 20 minutes. After 30 minutes at 0° C., it is slowly added to a solution of copper(I) bromide (25.1 g, 175 mmol) in 48% HBr/H2O (75 ml), while the temperature is kept below 5° C. After the addition is complete, the suspension is stirred at RT for 2 hours and then at 85° C. for 5 minutes. After cooling to RT, the mixture is extracted with CH2Cl2/MeOH (95:5, 800 ml). The organic layer is washed with saturated aqueous NaCl solution, dried over Na2SO4 and concentrated. Purification by FCC (hexane/EtOAc 4:1) affords the title compound. 1H NMR (DMSO, 400 MHz) δ 2.61 (s, 3H), 4.03 (s, 3H), 6.56 (s, 3H), 7.46 (d, J=9 Hz, 1H), 8.05 (d, J=9 Hz, 1H); ES-MS: 303 [M+H]+.

Aufarbeitung

  1. customis kept below 5° C
  2. additionAfter the addition
  3. waitat 85° C. for 5 minutes
  4. temperatureAfter cooling to RT
  5. extractionthe mixture is extracted with CH2Cl2/MeOH (95:5, 800 ml)
  6. washThe organic layer is washed with saturated aqueous NaCl solution
  7. dry with materialdried over Na2SO4
  8. concentrationconcentrated
  9. customPurification by FCC (hexane/EtOAc 4:1)

Quellen und Nachweise

ORD-Eintrag
ord-53f52f67c96149b7af108aea11d2cb73
Quelldatensatz
uspto-grants-2010_10
Patentnummer
US07820672B2

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