Water → HCID 23393870, compound

HRID 966473Notes

Reaction equation

HRID 966473 reaction equation
[H-].[Na+].[CH2:3]([O:10][C:11]([C:13]1[C:21]2[C:16](=[CH:17][CH:18]=[C:19]([O:22][CH2:23][CH2:24][Cl:25])[CH:20]=2)[NH:15][C:14]=1[CH3:26])=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.[CH3:27]I.O>CN(C=O)C>[CH2:3]([O:10][C:11]([C:13]1[C:21]2[C:16](=[CH:17][CH:18]=[C:19]([O:22][CH2:23][CH2:24][Cl:25])[CH:20]=2)[N:15]([CH3:27])[C:14]=1[CH3:26])=[O:12])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1

Participants

6

Reactant 4

HCID 962WaterHCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 23393871HCID 23393871, compound

Product 1

HCID 23393870HCID 23393870, compoundYield 69.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a suspension of NaH (0.959 mmol, 0.038 g, 60% in mineral oil, rinsed twice with hexanes) in 5 mL of DMF at 0° C. under N2 was added a solution of 5-(2-chloro-ethoxy)-2-methyl-1H-indole-3-carboxylic acid benzyl ester (0.873 mmol, 0.300 g, Example 1, Step A) in 3.73 mL of DMF. The ice bath was removed and the solution was stirred for 2 hours at room temperature. Methyl iodide (0.959 mmol, 0.060 mL, Aldrich) was added dropwise via syringe and the solution was stirred for 20 hours. Water (10 mL) was added and the mixture was stirred for 30 minutes. The resulting precipitate was filtered off, the filtrate was extracted with ether (3×10 mL), and the extracts were washed with water (2×10 mL), brine (1×10 mL), dried over MgSO4, and concentrated. The residue was combined with the solid and purified by silica gel flash column chromatography (30% ethyl acetate/hexanes) to give a white solid (0.216 g, 69%): 1HNMR (400 MHz, DMSO-d6) δ 2.67 (s, 3H, ArCH3), 3.66 (s, 3H, NCH3), 3.87-3.89 (m, 2H, CH2Cl), 4.09-4.12 (m, 2H, CH2OAr), 5.29 (s, 2H, CO2CH2Ph), 6.80-6.83 (m, 1H, ArH), 7.21-7.50 (m, 7H, ArH); MS(APCI+): m/z 358.0 (M+1).

Workup

  1. washrinsed twice with hexanes) in 5 mL of DMF at 0° C. under N2
  2. customThe ice bath was removed
  3. stirringthe solution was stirred for 20 hours
  4. stirringthe mixture was stirred for 30 minutes
  5. filtrationThe resulting precipitate was filtered off
  6. extractionthe filtrate was extracted with ether (3×10 mL)
  7. washthe extracts were washed with water (2×10 mL), brine (1×10 mL)
  8. dry with materialdried over MgSO4
  9. concentrationconcentrated
  10. custompurified by silica gel flash column chromatography (30% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-d51f1e63702540deb71eab25ac67b867
Source dataset
uspto-grants-2005_10
Patent number
US06951848B2

Reaction notes

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