Methyl iodide → 3-Bromo-5-chloro-1-methyl-1H-indole

HRID 80176Notes

Reaction equation

HRID 80176 reaction equation
C([O-])([O-])=O.[K+].[K+].[Br:7][C:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([Cl:17])[CH:15]=2)[NH:10][CH:9]=1.CI.[CH2:20](OC(=O)C)C>CN(C=O)C.CCCCCC>[Br:7][C:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([Cl:17])[CH:15]=2)[N:10]([CH3:20])[CH:9]=1

Participants

7

Reactant 4

HCID 6328Methyl iodideHCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 27629683-bromo-5-chloro-1H-indole

Product 1

HCID 687874273-Bromo-5-chloro-1-methyl-1H-indoleYield 65%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8058HexaneSolvent

Procedure

K2CO3 (1.39 g, 10.08 mmol) was added to a stirred solution of 3-bromo-5-chloro-1H-indole (775 mg, 3.36 mmol) in DMF (7.5 mL) and the resulting mixture was stirred for 30 minutes. This was followed by the addition of methyl iodide (572.5 mg, 4.03 mmol) at 0-5° C. and the stirring was continued for a further 2 hours at room temperature. The reaction was monitored by TLC (10% ethylacetate in hexane). The reaction mixture was partitioned between ice water and DCM. The organic layer was concentrated to afford the crude product. Purification by column chromatography on silica gel (5% ethylacetate in hexane) afforded 530 mg of 3-Bromo-5-chloro-1-methyl-1H-indole (65% yield).

Workup

  1. waitthe stirring was continued for a further 2 hours at room temperature
  2. customThe reaction mixture was partitioned between ice water and DCM
  3. concentrationThe organic layer was concentrated
  4. customto afford the crude product
  5. customPurification by column chromatography on silica gel (5% ethylacetate in hexane)

Sources & evidence

ORD record
ord-bed5129ed5d94698a306a264683945d3
Source dataset
uspto-grants-2014_09
Patent number
USRE045173E1

Reaction notes

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