1-Bromo-3-chloropropane → tert-butyl 1-(3-chloropropyl)-1H-indole-2-carboxylate

HRID 2362982Notes

Reaction equation

HRID 2362982 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11].[H-].[Na+].Br[CH2:20][CH2:21][CH2:22][Cl:23]>>[Cl:23][CH2:22][CH2:21][CH2:20][N:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[C:2]1[C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11]

Participants

4

Reactant 3

HCID 80061-Bromo-3-chloropropaneHCID 24758Sodium hydride2×HCID 11458614Boc-indole

Product 1

HCID 58046682tert-butyl 1-(3-chloropropyl)-1H-indole-2-carboxylateYield 104.7%

Conditions

Temperature
60 °C

Procedure

To a cold solution of tert-butyl 1H-indole-2-carboxylate (1.15 g, 4.94 mmol, 1 equiv) in dimthylformamide sodium hydride (60% dispersion) (237 mg, 5.92 mmol, 1.2 equiv) was added and the reaction stirred until all the sodium hydride has been consumed. 1-bromo-3-chloropropane (1.46 ml, 14.88 mmol, 3 equiv) was added and the reaction stirred at 60° C. for 16 h. The reaction was partitioned between ethyl acetate and water. The organic layer was further washed with brine, dried over MgSO4, filtered and concentrated in vacuo. The resulting residue was purifed using the Biotage flash chromatography system (SNAP, 50 g cartridge, Rf=0.5, gradient—5%-25% ethyl acetate in hexanes) to afford the title compound as an oil (1.52 g, quant); MS for C16H20ClNO2 m/z 293.12 (M+H)+.

Workup

  1. customhas been consumed
  2. customThe reaction was partitioned between ethyl acetate and water
  3. washThe organic layer was further washed with brine
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-d89d4709e3da4968bd5f97b99ffd0b23
Source dataset
uspto-grants-2014_04
Patent number
US08691836B2

Reaction notes

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