Hydrochloric Acid → [2-(1H-indol-5-ylsulfanyl)-benzyl]-methyl-amine

HRID 229850

反応式

HRID 229850 の反応式
C(OC([N:8]1[C:16]2[C:11](=[CH:12][C:13]([S:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[CH2:24][N:25](C(OC(C)(C)C)=O)[CH3:26])=[CH:14][CH:15]=2)[CH:10]=[CH:9]1)=O)(C)(C)C.Cl>CO.C(OCC)C>[NH:8]1[C:16]2[C:11](=[CH:12][C:13]([S:17][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[CH2:24][NH:25][CH3:26])=[CH:14][CH:15]=2)[CH:10]=[CH:9]1

参加物

5

反応物 2

HCID 313Hydrochloric AcidHCID 670184465-{2-[(Tert-butoxycarbonyl-methyl-amino)-methyl]-phenylsulfanyl}-indole-1-carboxylic acid tert-butyl ester

生成物 1

HCID 57461282[2-(1H-indol-5-ylsulfanyl)-benzyl]-methyl-amine収率 10.4%

試薬・触媒・溶媒 2

HCID 887Methanol溶媒HCID 3283Diethyl Ether溶媒

実験手順

(2-Mercapto-benzyl)-methyl-carbamic acid tert-butyl ester (1.85 g, 7.30 mmol) in dry toluene (15 mL) is placed in an Emrys Optimizer EXP 20 mL tube. Tris(dibenzylideneacetone) dipalladium (334 mg, 0.37 mmol), bis(2-diphenylphosphinophenyl)ether (197 mg, 0.37 mmol), tert-butyl-5-bromoindole-1-carboxylate (2.38 g, 8.03 mmol) and potassium tert-butoxide (860 mg, 7.67 mmol) are added. The reaction vessel is sealed and subjected to microwave heating at 160° C. for 15 minutes. Upon cooling the mixture is poured onto a plug of silica and the product is eluted with ethyl acetate-heptane (1:4). 0.67 g (20%) of 5-{2-[(tert-butoxycarbonyl-methyl-amino)-methyl]-phenylsulfanyl}-indole-1-carboxylic acid tert-butyl ester is isolated and used in the next step whithout further purification. 5-{2-[(tert-butoxycarbonyl-methyl-amino)-methyl]-phenylsulfanyl}-indole-1-carboxylic acid tert-butyl ester (0.67 g, 1.43 mmol) in methanol (15 mL) and diethyl ether saturated with hydrochloric acid (15 mL) is stirred at room temperature for 1 hour and concentrated in vacuo. Ice/water is added to the remanence and 28% aqueous NaOH is added until pH 9. The aqueous fraction is extracted with ethyl acetate (3×15 mL). Combined organic fractions are dried with MgSO4 and concentrated in vacuo. The product is purified by silica gel chromatography eluting with ethyl acetate-triethyl amine (100:4) followed by ethyl acetate-ethanol-triethyl amine (100:5:5). Upon evaporation of the volatiles, 40 mg (10%) of [2-(1H-indol-5-ylsulfanyl)-benzyl]-methyl-amine is isolated.

後処理

  1. customused in the next step whithout further purification
  2. concentrationconcentrated in vacuo
  3. additionIce/water is added to the remanence and 28% aqueous NaOH
  4. additionis added until pH 9
  5. extractionThe aqueous fraction is extracted with ethyl acetate (3×15 mL)
  6. dry with materialCombined organic fractions are dried with MgSO4
  7. concentrationconcentrated in vacuo
  8. customThe product is purified by silica gel chromatography
  9. washeluting with ethyl acetate-triethyl amine (100:4)
  10. customUpon evaporation of the volatiles

出典と根拠

ORDレコード
ord-7247554c799545f9bcb9553886358e00
出典データセット
uspto-grants-2009_07
特許番号
US07563908B2

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