Triethylamine → Indole

HRID 1459411Notes

Reaction equation

HRID 1459411 reaction equation
CS(Cl)(=O)=O.C([N:8]([CH2:11][CH3:12])[CH2:9][CH3:10])C.C(O[CH2:17][CH3:18])(=O)C.C([O-])([O-])=O.[Na+].[Na+].C(Cl)Cl.[CH3:28][C:29]#N>CC(O)C.CC#N>[NH:8]1[C:9]2[C:10](=[CH:28][CH:29]=[CH:17][CH:18]=2)[CH:12]=[CH:11]1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 31297Methanesulfonyl chlorideHCID 21877088Acetonitrile methylene chloride

Product 1

HCID 798IndoleYield 57%

Reagents, catalysts & solvents 2

HCID 3776IsopropanolSolventHCID 6342AcetonitrileSolvent

Procedure

Methane sulphonyl chloride (0.12 g, 1.07 mmol) was added to a solution of Intermediate 3 (0.2 g, 0.71 mmol) and triethylamine (0.143 g, 1.4 mmol) in CH2Cl2 /CH3CN (5 ml/5 ml), at 0° C. The mixture was warmed to room temperature and stirred for 1 h before adding ethyl acetate (30 ml) and washing the solution with saturated NaHCO3 solution (x1) and brine (x1). The organic was dried (MgSO4) and evaporated. To a solution of the resultant residue in IPA (25 ml) and CH3CN (3 ml) was added Intermediate 2 (0.36 g, 1.6 mmol) and Na2CO3 (0.12 g, 1.09 mmol). The mixture was heated at reflux for 8 h then cooled to room temperature and filtered. The solvent was removed under vacuum and the residue chromatographed on silica gel eluting with CH2Cl2 /MeOH/NH3 (90:8:1) to give the title-indole (0.208 g, 57%). The 2.0 hydrogen oxalate monohydrate salt was prepared, mp 213°-215° C., (Found: C, 52.54, H, 6.04, N, 9.50. C27 H37N5SO3. 2 (C2H2O4).1H2O requires C, 52.46, H, 6.11, N, 9.87%), m/e 511 (M)+, δ(360 MHz, D6 -DMSO) 1.88-2.00 (2H, m, CH2), 2.02 (3H, s, NHCOMe), 2.54 (3H, d, J=4.1 Hz, SO2NHMe), 2.68-3.12 (16H, m, 8 of CH2), 4.34 (2H, s, CH2), 6.79 (1H, br q, SO2NHMe), 7.09 (1H, dd, J=2.0 and 8.3 Hz, Ar-H), 7.15 (2H, d, J=8.5 Hz, Ar-H), 7.18 (1H, d, J=2.0 Hz, Ar-H), 7.33 (1H, d, J=8.3 Hz, Ar-H), 7.48 (2H, d, J=8.5Hz, Ar-H), 7.51 (1H, s, Ar-H), 9.87 (1H, s, NH), 10.89 (1H, s, NH).

Workup

  1. washwashing the solution with saturated NaHCO3 solution (x1) and brine (x1)
  2. dry with materialThe organic was dried (MgSO4)
  3. customevaporated
  4. temperatureThe mixture was heated
  5. temperatureat reflux for 8 h
  6. temperaturethen cooled to room temperature
  7. filtrationfiltered
  8. customThe solvent was removed under vacuum
  9. customthe residue chromatographed on silica gel eluting with CH2Cl2 /MeOH/NH3 (90:8:1)

Sources & evidence

ORD record
ord-a7aba3d3314647dbbc149317cba39be6
Source dataset
uspto-grants-1998_12
Patent number
US05854247

Reaction notes

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