N,N,N',N'-Tetramethylazodicarboxamide → [rac]-(4-{2-Methyl-1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-propoxy}-indol-1-yl)-acetic acid tert-butyl ester

HRID 1767876Notes

Reaction equation

HRID 1767876 reaction equation
[C:1]([O:5][C:6](=[O:18])[CH2:7][N:8]1[C:16]2[C:11](=[C:12]([OH:17])[CH:13]=[CH:14][CH:15]=2)[CH:10]=[CH:9]1)([CH3:4])([CH3:3])[CH3:2].[CH3:19][CH:20]([CH3:39])[CH:21]([C:23]1[S:27][C:26]([C:28]2[CH:33]=[CH:32][C:31]([C:34]([F:37])([F:36])[F:35])=[CH:30][CH:29]=2)=[N:25][C:24]=1[CH3:38])O.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](=[C:12]([O:17][CH:21]([C:23]3[S:27][C:26]([C:28]4[CH:33]=[CH:32][C:31]([C:34]([F:36])([F:37])[F:35])=[CH:30][CH:29]=4)=[N:25][C:24]=3[CH3:38])[CH:20]([CH3:39])[CH3:19])[CH:13]=[CH:14][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 22647459[Rac]-2-methyl-1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl)-propan-1-olHCID 69279689tert-Butyl (4-hydroxy-1H-indol-1-yl)acetate

Product 1

HCID 69279682[rac]-(4-{2-Methyl-1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-propoxy}-indol-1-yl)-acetic acid tert-butyl esterYield 12%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To an ice cold solution of (4-hydroxy-indol-1-yl)-acetic acid tert-butyl ester (49 mg, 0.2 mmol), [rac]-2-methyl-1-[4-methyl-2-(4-trifluoromethyl-phenyl)-thiazol-5-yl]-propan-1-ol [62 mg, 0.2 mmol; PCT Int. Appl. (2002), WO 02/062774 A1] and tributylphosphine (70 μl, 0.3 mmol) in tetrahydrofuran (3 ml) was added N,N,N′,N′-tetramethyl azodicarboxamide (51 mg, 0.3 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 13 mg (24 μmol, 12%) of the title compound as yellow oil.

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-6d2443345e8b4afebb5ab4f69440a17c
Source dataset
uspto-grants-2007_06
Patent number
US07235572B2

Reaction notes

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