Sodium hydride → Methyl 3-cyclohexyl-1-(5-methoxy-5-oxopentyl)-1H-indole-6-carboxylate

HRID 860727Notes

Reaction equation

HRID 860727 reaction equation
[CH:1]1([C:7]2[C:15]3[C:10](=[CH:11][C:12]([C:16]([O:18][CH3:19])=[O:17])=[CH:13][CH:14]=3)[NH:9][CH:8]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].Br[CH2:23][CH2:24][CH2:25][CH2:26][C:27]([O:29][CH3:30])=[O:28]>CN(C=O)C>[CH:1]1([C:7]2[C:15]3[C:10](=[CH:11][C:12]([C:16]([O:18][CH3:19])=[O:17])=[CH:13][CH:14]=3)[N:9]([CH2:23][CH2:24][CH2:25][CH2:26][C:27]([O:29][CH3:30])=[O:28])[CH:8]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 79557Methyl 5-bromovalerateHCID 11230631Methyl 3-cyclohexyl-1H-indole-6-carboxylate

Product 1

HCID 56590628Methyl 3-cyclohexyl-1-(5-methoxy-5-oxopentyl)-1H-indole-6-carboxylateYield 57%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Methyl 3-cyclohexyl-1H-indole-6-carboxylate (500 mg, 1.94 mmol) was added to a suspension of NaH (85.5 mg of 60% dispersion in mineral oil, 2.14 mmol) in DMF (5 mL), and the reaction mixture stirred at RT for 15 min. Methyl 5-bromovalerate (0.305 mL, 2.14 mmol) was then added and the reaction mixture stirred at RT overnight, after which the reaction was quenched with ice and extracted with ethyl acetate (2×50 mL). The extracts were then combined, washed with 1N HCl solution, dried (MgSO4), filtered and concentrated in vacuo. The residue was purified by silica gel flash chromatography using hexanes to 25% ethyl acetate in hexanes as eluant to give the title compound as a colorless thick oil (0.41 g, 57% yield). MS m/z 372(MH+). 1H NMR (300 MHz, CDCl3) □ ppm 1.23 (m, 1 H) 1.35–1.48 (m, 5 H) 1.62 (m, 2 H) 1.69–1.89 (m, 6 H) 2.03 (m, 2 H) 2.29 (t, J=7.32 Hz, 2 H) 2.78 (m, 1 H) 3.62 (s, 3 H) 3.90 (s, 3 H) 4.11 (t, J=6.95 Hz, 2 H) 6.97 (s, 1 H) 7.60 (d, J=8.42 Hz, 1 H) 7.72 (d, J=9.51 Hz, 1 H) 8.00 (s, 1 H).

Workup

  1. stirringthe reaction mixture stirred at RT overnight
  2. customafter which the reaction was quenched with ice
  3. extractionextracted with ethyl acetate (2×50 mL)
  4. washwashed with 1N HCl solution
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by silica gel flash chromatography

Sources & evidence

ORD record
ord-c1e6d7cd96c64236993c04403d5c7202
Source dataset
uspto-grants-2006_12
Patent number
US07153848B2

Reaction notes

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