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

HRID 392773ノート

反応式

HRID 392773 の反応式
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

参加物

6

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 2

HCID 702Ethanol溶媒HCID 962Water溶媒

実験手順

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]+.

後処理

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

出典と根拠

ORDレコード
ord-d35d9668240d4a00937b14ee7273320c
出典データセット
uspto-grants-2004_10
特許番号
US06803362B2

反応ノート

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