Sodium hydride → 1-cyclohexylmethyl-1H-indole-6-carboxylic acid methyl ester

HRID 1395883Notes

Reaction equation

HRID 1395883 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:13]=[C:12]2[C:8]([CH:9]=[CH:10][NH:11]2)=[CH:7][CH:6]=1)=[O:4].[CH:14]1([CH2:20]Br)[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]1.[H-].[Na+]>CN(C=O)C.O.C(OCC)(=O)C>[CH3:1][O:2][C:3]([C:5]1[CH:13]=[C:12]2[C:8]([CH:9]=[CH:10][N:11]2[CH2:20][CH:14]2[CH2:19][CH2:18][CH2:17][CH2:16][CH2:15]2)=[CH:7][CH:6]=1)=[O:4]

Participants

7

Reactant 3

HCID 24758Sodium hydrideHCID 137636Cyclohexane, (bromomethyl)-HCID 639844Methyl indole-6-carboxylate

Product 1

HCID 109785681-cyclohexylmethyl-1H-indole-6-carboxylic acid methyl esterYield 74%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of commercially available 1H-indole-6-carboxylic acid methyl ester (0.35 g, 2.0 mmol) and cyclohexylmethyl bromide (0.31 mL, 2.2 mmol) in DMF (2 mL) was added sodium hydride (92 mg, 2.3 mmol). After stirring at room temperature for 3 hr, the solution was diluted with water (25 mL) and ethyl acetate (75 mL), the organic layer was washed again with dilute NaHCO3 (25 mL) and then brine (25 mL). The organic layer was dried over Na2SO4, filtered and concentrated. The remaining residue was subjected to flash chromatography (ethyl acetate/hexane, 1:24) to provide 1-cyclohexylmethyl-1H-indole-6-carboxylic acid methyl ester as a white solid (0.40 g, 74% yield). 1H NMR (400 MHz, DMSO) δ 8.10 (s, 1H), 7.62 (m, 2W), 7.58 (d, 1H, J=3.1 Hz), 6.52 (d, 1H, J=3.1 Hz), 4.10 (d, 2H, J=7.4 Hz), 3.85 (s, 3H), 1.77 (m, 1H), 1.65-1.57 (m 3H), 1.46 (m, 2H), 1.19 (m, 3H), 0.98 (m, 2H).

Workup

  1. washthe organic layer was washed again with dilute NaHCO3 (25 mL)
  2. dry with materialThe organic layer was dried over Na2SO4
  3. filtrationfiltered
  4. concentrationconcentrated

Sources & evidence

ORD record
ord-3a3a7bf47a5a461b9817eb1e7e8b8f95
Source dataset
uspto-grants-2014_12
Patent number
US08900565B2

Reaction notes

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