Methyl iodide → 5-(Benzoyl-methyl-amino)-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester

HRID 2361893Notes

Reaction equation

HRID 2361893 reaction equation
[H-].[Na+].[C:3]([O:7][C:8]([N:10]1[C:18]2[C:13](=[CH:14][C:15]([NH:19][C:20](=[O:27])[C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[CH:16][CH:17]=2)[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:5])[CH3:4].[CH3:28]I>CN(C=O)C.C([O-])(O)=O.[Na+]>[C:3]([O:7][C:8]([N:10]1[C:18]2[C:13](=[CH:14][C:15]([N:19]([C:20](=[O:27])[C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)[CH3:28])=[CH:16][CH:17]=2)[CH2:12][CH2:11]1)=[O:9])([CH3:6])([CH3:4])[CH3:5]

Participants

6

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 668890921h-Indole-1-carboxylic acid,5-(benzoylamino)-2,3-dihydro-,1,1-dimethylethyl ester

Product 1

HCID 668917365-(Benzoyl-methyl-amino)-2,3-dihydro-indole-1-carboxylic acid tert-butyl esterYield 93%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 516892Sodium BicarbonateSolvent

Procedure

Sodium hydride (60 mg, 1.5 eq.) was added to a mixture of 5-benzoylamino-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester (570 mg, 1.68 mmol) and methyl iodide (0.42 mL, 4.0 eq.) in DMF (10 mL) at 0° C. and the resulting mixture was stirred for 20 min. After concentration, the residue from reaction mixture was diluted with sat. NaHCO3 and extracted with 3×EtOAc. The combined extracts were dried over Na2SO4, filtered, concentrated and the product was purified by chromatography (30% EtOAc-hexanes) to give 5-(benzoyl-methyl-amino)-2,3-dihydro-indole-1-carboxylic acid tert-butyl ester (547 mg, 93%).

Workup

  1. concentrationAfter concentration
  2. customthe residue from reaction mixture
  3. extractionextracted with 3×EtOAc
  4. dry with materialThe combined extracts were dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customthe product was purified by chromatography (30% EtOAc-hexanes)

Sources & evidence

ORD record
ord-d3953909f8244611a07e89957ee30a96
Source dataset
uspto-grants-2014_04
Patent number
US08691814B2

Reaction notes

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