Hydrochloric Acid → 4,5-dichloro-1H-indole-2-carboxylic acid

HRID 392773Notes

Reaction equation

HRID 392773 reaction equation
C([O:3][C:4]([C:6]1[NH:7][C:8]2[C:13]([CH:14]=1)=[C:12]([Cl:15])[C:11]([Cl:16])=[CH:10][CH:9]=2)=[O:5])C.[OH-].[Li+].Cl>C(O)C.O>[Cl:15][C:12]1[C:11]([Cl:16])=[CH:10][CH:9]=[C:8]2[C:13]=1[CH:14]=[C:6]([C:4]([OH:5])=[O:3])[NH:7]2

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 3939Lithium HydroxideHCID 4714971ethyl 4,5-dichloro-1H-indole-2-carboxylate

Product 1

HCID 36148594,5-dichloro-1H-indole-2-carboxylic acidYield 60.6%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Procedure

4,5-Dichloro-1H-indole-2-carboxylic acid ethyl ester (0.5 g) was treated with 1 M lithium hydroxide in ethanol (3 mL) and heated, water bath, for 2 h. The solution was acidified with 10% hydrochloric acid, diluted with water and extracted with ethylacetate. The organic extracts were combined, dried over sodium sulfate and filtered, and solvent was evaporated to give 4,5-dichloro-1H-indole-2-carboxylic acid (0.27 g, 60%). This material was treated with -ethyl-3-(3′-dimethylaminopropyl)-carbodiimide hydrochloride (0.5 g), HOBT (0.4 g) and N,N-diisopropylethylamine (1 mL) in DMF (2 mL) and dichloromethane (2 mL) was treated with N-methylpiperazine (0.2 mL) stirred at ambient temperature for 18 h then diluted with water. The organic portion was separated, washed with brine, dried over sodium sulfate, and filtered. Solvent was removed under reduced pressure, and the residue was purified via silica gel chromatography (3-8% 2 M ammonia in methanol/dichloromethane) to give the title compound (0.15 g, 40%). 1H NMR (400 MHz, CDCl3): δ 10.2 (br.s, 1H), 7.25-7.16 (m, 2H), 6.75 (d, J=2 Hz, 1H), 3.92 (br.m, 4H), 2.47 (m, 4H), 2.30 (s, 3H). MS (electrospray): exact mass calculated for C14H15Cl2N3O, 311.06; m/z found, 312.0 [M+H]+.

Workup

  1. temperatureheated
  2. extractionextracted with ethylacetate
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. customsolvent was evaporated

Sources & evidence

ORD record
ord-d35d9668240d4a00937b14ee7273320c
Source dataset
uspto-grants-2004_10
Patent number
US06803362B2

Reaction notes

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