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

HRID 1751056Notes

Reaction equation

HRID 1751056 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 purified 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
  7. customThe resulting residue was purified

Sources & evidence

ORD record
ord-c9ceaf2c1a40496f882f87cc6ff880d3
Source dataset
uspto-grants-2015_10
Patent number
US09156840B2

Reaction notes

Loading…