Methyl iodide → methyl 2-[2-(benzyloxy)phenyl]-3-cyclohexyl-1-methyl-1H-indole-6-carboxylate

HRID 1807630Notes

Reaction equation

HRID 1807630 reaction equation
[H-].[Na+].[CH2:3]([O:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[C:17]1[NH:18][C:19]2[C:24]([C:25]=1[CH:26]1[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1)=[CH:23][CH:22]=[C:21]([C:32]([O:34][CH3:35])=[O:33])[CH:20]=2)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.I[CH3:37]>CN(C=O)C>[CH2:3]([O:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[C:17]1[N:18]([CH3:37])[C:19]2[C:24]([C:25]=1[CH:26]1[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1)=[CH:23][CH:22]=[C:21]([C:32]([O:34][CH3:35])=[O:33])[CH:20]=2)[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 67225298methyl 2-[2-(benzyloxy)phenyl]-3-cyclohexyl-1H-indole-6-carboxylate

Product 1

HCID 58317811methyl 2-[2-(benzyloxy)phenyl]-3-cyclohexyl-1-methyl-1H-indole-6-carboxylateYield 80.4%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

NaH (810 mg, 32.1 mmol) was added to a solution of intermediate 2 (9.4 g, 21.4 mmol) in dry DMF. Then, iodomethane (3.64 g, 25.7 mmol) was added at room temperature. After 12 h, the reaction mixture was partitioned between water (pH 6) and AcOEt. Organic layer was dried over anhydrous Na2SO4, filtered and then evaporated. The residue was purified by silica column chromatography (gradient heptane/AcOEt 1:0 to 80:20) to yield 7.8 g (80%) of methyl 2-[2-(benzyloxy)phenyl]-3-cyclohexyl-1-methyl-1H-indole-6-carboxylate 3: m/z=454 (M+H)+.

Workup

  1. customthe reaction mixture was partitioned between water (pH 6) and AcOEt
  2. dry with materialOrganic layer was dried over anhydrous Na2SO4
  3. filtrationfiltered
  4. customevaporated
  5. customThe residue was purified by silica column chromatography (gradient heptane/AcOEt 1:0 to 80:20)

Sources & evidence

ORD record
ord-bbda16bac2334743a156ca682f43213c
Source dataset
uspto-grants-2013_01
Patent number
US08357687B2

Reaction notes

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