Acetonitrile → {6-[2,2-Dimethyl-5-(4-trifluoromethoxy-phenyl)-pent-4-ynyloxy]-indol-1-yl}-acetic acid ethyl ester

HRID 751201Notes

Reaction equation

HRID 751201 reaction equation
[CH3:1][C:2]([CH3:19])([CH2:5][C:6]#[C:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][C:15]([F:18])([F:17])[F:16])=[CH:10][CH:9]=1)[CH2:3][OH:4].F[C:21](F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.C([C:39]1[CH:44]=[CH:43][CH:42]=[C:41]([C:45]([CH3:48])([CH3:47])C)[N:40]=1)(C)(C)C.[C:49](=[O:52])([O-])[O-:50].[Cs+].[Cs+].[C:55](#N)[CH3:56]>ClCCl>[CH2:55]([O:50][C:49](=[O:52])[CH2:21][N:40]1[C:41]2[C:45](=[CH:47][CH:44]=[C:43]([O:4][CH2:3][C:2]([CH3:19])([CH3:1])[CH2:5][C:6]#[C:7][C:8]3[CH:13]=[CH:12][C:11]([O:14][C:15]([F:16])([F:17])[F:18])=[CH:10][CH:9]=3)[CH:42]=2)[CH:48]=[CH:39]1)[CH3:56]

Participants

7

Reactant 5

HCID 6342AcetonitrileHCID 10796Cesium carbonateHCID 67749Trifluoromethanesulfonic anhydrideHCID 685102,6-Di-tert-butylpyridineHCID 688212542,2-Dimethyl-5-(4-trifluoromethoxy-phenyl)-pent-4-yn-1-ol

Product 1

HCID 68822721{6-[2,2-Dimethyl-5-(4-trifluoromethoxy-phenyl)-pent-4-ynyloxy]-indol-1-yl}-acetic acid ethyl esterYield 40%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To an ice cold solution of 2,2-dimethyl-5-(4-trifluoromethoxy-phenyl)-pent-4-yn-1-ol (50 mg, 0.18 mmol) in dichloromethane (180 μl) was added trifluoromethanesulfonic anhydride (30 μl, 0.2 mmol) and 2,6-di-tert-butylpyridine (50 μl, 0.22 mmol) under an argon atmosphere. The reaction mixture was stirred for 2 h while the temperature rose from 0° C. to ambient temperature. The solvent was removed under reduced pressure and the residue dissolved in acetonitrile (0.6 ml). The obtained solution was added to a suspension of (6-hydroxy-indol-1-yl)-acetic acid ethyl ester (40 mg, 0.18 mmol; example 1 c]) and cesium carbonate (126 mg, 0.39 mmol) in acetonitrile (1.2 ml). The reaction mixture was stirred for 12 h at ambient temperature and for 1 h under reflux conditions. The residue was filtered off and washed with acetonitrile. The filtrate was brought to dryness under reduced pressure and the residue was dissolved in dichloromethane. The solvent was removed under reduced pressure and the remaining brown oil was purified by flash chromatography (silica gel, heptane/AcOEt) to give 35 mg (70 μmol, 40%) of the title compound as colorless oil.

Workup

  1. customrose from 0° C. to ambient temperature
  2. customThe solvent was removed under reduced pressure
  3. dissolutionthe residue dissolved in acetonitrile (0.6 ml)
  4. additionThe obtained solution was added to a suspension of (6-hydroxy-indol-1-yl)-acetic acid ethyl ester (40 mg, 0.18 mmol
  5. stirringThe reaction mixture was stirred for 12 h at ambient temperature and for 1 h under reflux conditions
  6. filtrationThe residue was filtered off
  7. washwashed with acetonitrile
  8. dissolutionthe residue was dissolved in dichloromethane
  9. customThe solvent was removed under reduced pressure
  10. customthe remaining brown oil was purified by flash chromatography (silica gel, heptane/AcOEt)

Sources & evidence

ORD record
ord-fc47bbfd20f44ea8a75e7df24deeb86c
Source dataset
uspto-grants-2008_07
Patent number
US07405236B2

Reaction notes

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