2-Chloroethanol → 4-(2-chloroethoxy)-1H-indole

HRID 896288Notes

Reaction equation

HRID 896288 reaction equation
[OH:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2.[Cl:11][CH2:12][CH2:13]O.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N(C(OCC)=O)=NC(OCC)=O>O1CCCC1.CCOCC.CCCCCC.C(OCC)C>[Cl:11][CH2:12][CH2:13][O:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]2

Participants

8

Reactant 4

HCID 342-ChloroethanolHCID 11776TriphenylphosphineHCID 754211H-indol-4-olHCID 220568ethyl N-ethoxycarbonyliminocarbamate

Product 1

HCID 106317214-(2-chloroethoxy)-1H-indole

Reagents, catalysts & solvents 3

HCID 3283Diethyl EtherSolventHCID 8028TetrahydrofuranSolventHCID 21584099Diethylether hexaneSolvent

Procedure

A solution of 4-hydroxyindole (3.99 g, 30 mmol), 2-chloroethanol (6.03 ml, 90 mmol) and triphenylphosphine (23.6 g, 90 mmol) in tetrahydrofuran is treated with diethyl azodicarboxylate (14.1 ml, 90 mmol) under nitrogen at room temperature, stirred for 2 hr at room temperature and concentrated in vacuo to give a residue. Cooled diethyl ether is added to the residue and the solid triphenylphosphine oxide is precipitated and removed by filtration. The filtrate is concentrated and purified by flash chromatography (silica gel, EtOAc/hexane: 1.5/8.5) to give an oil. After trituration with Et2O/hexane (1/10), the title compound is obtained as a white solid, 4.8 g (82%) mp 60° C., identified by NMR and mass spectral analyses.

Workup

  1. concentrationconcentrated in vacuo
  2. customto give a residue
  3. customthe solid triphenylphosphine oxide is precipitated
  4. customremoved by filtration
  5. concentrationThe filtrate is concentrated
  6. custompurified by flash chromatography (silica gel, EtOAc/hexane: 1.5/8.5)
  7. customto give an oil

Sources & evidence

ORD record
ord-ec880388db014a8592369b86bcf1db4b
Source dataset
uspto-grants-2005_07
Patent number
US06919354B2

Reaction notes

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