Sodium Iodide → Indole

HRID 1419777Notes

Reaction equation

HRID 1419777 reaction equation
CS(Cl)(=O)=O.N1(C[C:12]2[CH:13]=[C:14]3[C:18](=[CH:19][CH:20]=2)[NH:17][CH:16]=[C:15]3CCCO)C=NC=N1.C(N(CC)CC)C.FC1C=C(CCN2CCNCC2)C=CC=1.C([O-])([O-])=O.[K+].[K+].[I-].[Na+]>C1COCC1>[NH:17]1[C:18]2[C:14](=[CH:13][CH:12]=[CH:20][CH:19]=2)[CH:15]=[CH:16]1

Participants

8

Reactant 6

HCID 5238Sodium IodideHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 31297Methanesulfonyl chlorideHCID 4715425HCID 4715425, compoundHCID 10729768HCID 10729768, compound

Product 1

HCID 798IndoleYield 267%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

Methanesulphonyl chloride (0.118 g, 1.03 mmol) was added to a stirred solution of 3-[5-(1,2,4-triazol-1-ylmethyl)-lH-indol-3-yl]propan-1-ol (0.22 g, 0.86 mmol) and triethylamine (0.104 g, 1.03 mmol), in anhydrous THF (30 ml) at +5° C. The solution was warmed to room temperature and stirred for 1.5 h. The solvent was removed under vacuum and the residue partitioned between CH2Cl2 (2×75 ml) and water (30 ml). The combined extracts were dried (Na2SO4) and evaporated and the residue redissolved in anhydrous THF (20 ml). To the solution was added 4-[2-(3-fluorophenyl)ethyl]piperazine (0.339 g, 1.63 mmol), K2CO3 (0.225 g, 1.63 mmol) and sodium iodide (0.245 g, 1.63 mmol) and the mixture refluxed for 2 h. The solvent was removed under vacuum and the residue partitioned between CH2Cl2 (2×100 ml) and water (40 ml). The combined extracts were dried (Na2SO4) and evaporated and the resulting residue chromatographed on silica gel eluting with CH2Cl2 /EtOH/NH3 (80:5:0.5) to give the title-indole (0.269 g, 70%). The dihydrogen maleate salt was prepared, mp 187° C., (Found: C, 60.01; H, 5.63; N, 12.12. C26H31N6F. 2(C4H4 04) requires C, 60.17; H, 5.79; N, 12.38%), m/e 447 (M+1)+, δ (360 MHz, D6 -DMSO) 1.90-2.02 (2H, m, CH2), 2.54-3.70 (16H, m, 8 of CH2), 5.44 (2H, s, CH2), 6.14 (maleate-H's), 7.00-7.14 (4H, m, Ar--H), 7.19 (1H, s, Ar--H), 7.31-7.36 (2H, m, Ar--H), 7.52 (1H, s, Ar--H), 7.95 (1H, s, Ar--H), 8.60 (1H, s, Ar--H), 10.90 (1H, s, NH).

Workup

  1. customThe solvent was removed under vacuum
  2. customthe residue partitioned between CH2Cl2 (2×75 ml) and water (30 ml)
  3. dry with materialThe combined extracts were dried (Na2SO4)
  4. customevaporated
  5. dissolutionthe residue redissolved in anhydrous THF (20 ml)
  6. temperaturethe mixture refluxed for 2 h
  7. customThe solvent was removed under vacuum
  8. customthe residue partitioned between CH2Cl2 (2×100 ml) and water (40 ml)
  9. dry with materialThe combined extracts were dried (Na2SO4)
  10. customevaporated
  11. customthe resulting residue chromatographed on silica gel eluting with CH2Cl2 /EtOH/NH3 (80:5:0.5)

Sources & evidence

ORD record
ord-d89d690aad864c809dd0590834ba34c0
Source dataset
uspto-grants-1999_03
Patent number
US05889008

Reaction notes

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