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

HRID 392773노트

반응식

HRID 392773 반응식
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

참가 물질

6

반응물 3

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

생성물 1

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

시약·촉매·용매 2

HCID 702Ethanol용매HCID 962Water용매

실험 절차

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]+.

후처리

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

출처 및 근거

ORD 기록
ord-d35d9668240d4a00937b14ee7273320c
출처 데이터셋
uspto-grants-2004_10
특허 번호
US06803362B2

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