N,N,N',N'-Tetramethylazodicarboxamide → {6-[2-Methyl-6-(4-trifluoromethyl-phenyl)-pyridin-3-ylmethoxy]-indol-1-yl}-acetic acid tert-butyl ester

HRID 890436Notes

Reaction equation

HRID 890436 reaction equation
[C:1]([O:5][C:6](=[O:18])[CH2:7][N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([OH:17])[CH:15]=2)[CH:10]=[CH:9]1)([CH3:4])([CH3:3])[CH3:2].[CH3:19][C:20]1[C:25]([CH2:26]O)=[CH:24][CH:23]=[C:22]([C:28]2[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=2)[N:21]=1.C(P(CCCC)CCCC)CCC.CN(C)C(N=NC(N(C)C)=O)=O>O1CCCC1>[C:1]([O:5][C:6](=[O:18])[CH2:7][N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[C:14]([O:17][CH2:26][C:25]3[C:20]([CH3:19])=[N:21][C:22]([C:28]4[CH:29]=[CH:30][C:31]([C:34]([F:37])([F:35])[F:36])=[CH:32][CH:33]=4)=[CH:23][CH:24]=3)[CH:15]=2)[CH:10]=[CH:9]1)([CH3:4])([CH3:2])[CH3:3]

Participants

6

Reactant 4

HCID 4278N,N,N',N'-TetramethylazodicarboxamideHCID 13831TributylphosphineHCID 21935862[2-Methyl-6-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-methanolHCID 69283069tert-Butyl (6-hydroxy-1H-indol-1-yl)acetate

Product 1

HCID 69642195{6-[2-Methyl-6-(4-trifluoromethyl-phenyl)-pyridin-3-ylmethoxy]-indol-1-yl}-acetic acid tert-butyl esterYield 75%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To an ice cold solution of (6-hydroxy-indol-1-yl)-acetic acid tert-butyl ester (70 mg, 0.28 mmol), [2-methyl-6-(4-trifluoromethyl-phenyl)-pyridin-3-yl]-methanol (76 mg, 0.28 mmol) and tributylphosphine (110 μl, 0.42 mmol) in tetrahydrofuran (4 ml) was added N,N,N′,N′-tetramethyl azodicarboxamide (73 mg, 0.42 mmol) under an argon atmosphere. The cooling bath was removed and stirring continued for 14 h. Filtration over celite and evaporation of the solvent under reduced pressure gave a yellow oil which was purified by column chromatography (silica gel, heptane/AcOEt) to give 105 mg (0.21 mmol, 75%) of the title compound as white crystals.

Workup

  1. customThe cooling bath was removed
  2. filtrationFiltration
  3. customover celite and evaporation of the solvent under reduced pressure
  4. customgave a yellow oil which
  5. customwas purified by column chromatography (silica gel, heptane/AcOEt)

Sources & evidence

ORD record
ord-1b1af166a4f74348ad6e91f9c0ea8997
Source dataset
uspto-grants-2006_02
Patent number
US06995263B2

Reaction notes

Loading…