N-Boc-5-bromoindole → 5-{2-[(Tert-butoxycarbonyl-methyl-amino)-methyl]-phenylsulfanyl}-indole-1-carboxylic acid tert-butyl ester

HRID 1994366

Reaction equation

HRID 1994366 reaction equation
[C:1]([O:5][C:6](=[O:17])[N:7]([CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[CH:12][C:11]=1[SH:16])[CH3:8])([CH3:4])([CH3:3])[CH3:2].C1(P(C2C=CC=CC=2)C2C=CC=CC=2OC2C=CC=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[C:57]([O:61][C:62]([N:64]1[C:72]2[C:67](=[CH:68][C:69](Br)=[CH:70][CH:71]=2)[CH:66]=[CH:65]1)=[O:63])([CH3:60])([CH3:59])[CH3:58].CC(C)([O-])C.[K+]>C1(C)C=CC=CC=1.[Pd].[Pd].C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1.C(=CC(C=CC1C=CC=CC=1)=O)C1C=CC=CC=1>[C:57]([O:61][C:62]([N:64]1[C:72]2[C:67](=[CH:68][C:69]([S:16][C:11]3[CH:12]=[CH:13][CH:14]=[CH:15][C:10]=3[CH2:9][N:7]([C:6]([O:5][C:1]([CH3:4])([CH3:2])[CH3:3])=[O:17])[CH3:8])=[CH:70][CH:71]=2)[CH:66]=[CH:65]1)=[O:63])([CH3:60])([CH3:58])[CH3:59]

Participants

7

Reactant 4

HCID 2728482N-Boc-5-bromoindoleHCID 4285986Bis[2-(diphenylphosphino)phenyl] etherHCID 23665647Potassium tert-butoxideHCID 67018450(2-Mercapto-benzyl)-methyl-carbamic acid tert-butyl ester

Product 1

HCID 670184465-{2-[(Tert-butoxycarbonyl-methyl-amino)-methyl]-phenylsulfanyl}-indole-1-carboxylic acid tert-butyl esterYield 20%

Reagents, catalysts & solvents 2

HCID 9832798Tris(dibenzylideneacetone) dipalladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
160 °C

Procedure

(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.

Workup

  1. customThe reaction vessel is sealed
  2. temperatureUpon cooling the mixture
  3. additionis poured onto a plug of silica
  4. washthe product is eluted with ethyl acetate-heptane (1:4)

Sources & evidence

ORD record
ord-c34c4f358645493b9e25ec0cb03a3ee6
Source dataset
uspto-grants-2010_01
Patent number
US07652150B2

Linked notes

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