Sodium hydride → Ethyl 1-((2'-(tert-butoxycarbonyl)biphenyl-4-yl)methyl)-2,3-dimethyl-1H-indole-5-carboxylate

HRID 1851880Notes

Reaction equation

HRID 1851880 reaction equation
[CH3:1][C:2]1[NH:3][C:4]2[C:9]([C:10]=1[CH3:11])=[CH:8][C:7]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:6][CH:5]=2.[H-].[Na+].Br[CH2:20][C:21]1[CH:26]=[CH:25][C:24]([C:27]2[C:28]([C:33]([O:35][C:36]([CH3:39])([CH3:38])[CH3:37])=[O:34])=[CH:29][CH:30]=[CH:31][CH:32]=2)=[CH:23][CH:22]=1>CN(C=O)C>[C:36]([O:35][C:33]([C:28]1[CH:29]=[CH:30][CH:31]=[CH:32][C:27]=1[C:24]1[CH:25]=[CH:26][C:21]([CH2:20][N:3]2[C:4]3[C:9](=[CH:8][C:7]([C:12]([O:14][CH2:15][CH3:16])=[O:13])=[CH:6][CH:5]=3)[C:10]([CH3:11])=[C:2]2[CH3:1])=[CH:22][CH:23]=1)=[O:34])([CH3:39])([CH3:38])[CH3:37]

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 612460Ethyl 2,3-dimethyl-1H-indole-5-carboxylateHCID 9906257tert-Butyl 4'-(bromomethyl)biphenyl-2-carboxylate

Product 1

HCID 71075103Ethyl 1-((2'-(tert-butoxycarbonyl)biphenyl-4-yl)methyl)-2,3-dimethyl-1H-indole-5-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

To a mixture of ethyl 2,3-dimethyl-1H-indole-5-carboxylate (1.493 g, 6.87 mmol) in dry DMF (10 mL) at 0° C. under argon was added NaH (0.3 g, 60% dispersion in mineral oil, 7.56 mmol) in portions. The reaction mixture was stirred at rt for 30 min and then re-cooled to 0° C. Tert-butyl 4′-(bromomethyl)biphenyl-2-carboxylate (2.62 g, 7.56 mmol) in DMF (2 mL) was slowly added. The reaction mixture was stirred at rt for another 1 h. The completion of the reaction was monitored by anal. HPLC. The reaction was quenched with MeOH, and then the solvent was removed in vacuo. The crude was dissolved in AcOEt, washed with saturated aqueous NaHCO3, brine and dried over Na2 SO4 and filtered. The filtrate was evaporated in vacuo to obtain the crude which was purified by flash chromatography (AcOEt/Hex 10→100%) to obtain the title compound. ESI-MS (m/z): 484 [M+H]+.

Workup

  1. temperaturere-cooled to 0° C
  2. stirringThe reaction mixture was stirred at rt for another 1 h
  3. customThe reaction was quenched with MeOH
  4. customthe solvent was removed in vacuo
  5. dissolutionThe crude was dissolved in AcOEt
  6. washwashed with saturated aqueous NaHCO3, brine
  7. customdried over Na2 SO4
  8. filtrationfiltered
  9. customThe filtrate was evaporated in vacuo
  10. customto obtain the crude which
  11. customwas purified by flash chromatography (AcOEt/Hex 10→100%)

Sources & evidence

ORD record
ord-653f27e8ef1e476db96dbc6254c3ca59
Source dataset
uspto-grants-2015_02
Patent number
US08957093B2

Reaction notes

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