N,N,N',N'-Tetramethylazodicarboxamide → 2-Methyl-2-{2-methyl-4-[2-methyl-6-(4-trifluoromethoxy-phenyl)-4-trifluoromethyl-pyridin-3-ylmethoxy]-phenoxy}-propionic acid ethyl ester

HRID 1242450Notes

Reaction equation

HRID 1242450 reaction equation
[CH2:1]([O:3][C:4](=[O:17])[C:5]([O:8][C:9]1[CH:14]=[CH:13][C:12]([OH:15])=[CH:11][C:10]=1[CH3:16])([CH3:7])[CH3:6])[CH3:2].[CH3:18][C:19]1[C:24]([CH2:25]O)=[C:23]([C:27]([F:30])([F:29])[F:28])[CH:22]=[C:21]([C:31]2[CH:36]=[CH:35][C:34]([O:37][C:38]([F:41])([F:40])[F:39])=[CH:33][CH:32]=2)[N:20]=1.C(P(CCCC)CCCC)CCC.CN(C)C(N=NC(N(C)C)=O)=O>O1CCCC1>[CH2:1]([O:3][C:4](=[O:17])[C:5]([CH3:6])([O:8][C:9]1[CH:14]=[CH:13][C:12]([O:15][CH2:25][C:24]2[C:19]([CH3:18])=[N:20][C:21]([C:31]3[CH:32]=[CH:33][C:34]([O:37][C:38]([F:40])([F:39])[F:41])=[CH:35][CH:36]=3)=[CH:22][C:23]=2[C:27]([F:28])([F:30])[F:29])=[CH:11][C:10]=1[CH3:16])[CH3:7])[CH3:2]

Participants

6

Reactant 4

HCID 4278N,N,N',N'-TetramethylazodicarboxamideHCID 13831TributylphosphineHCID 16756990Ethyl 2-(4-hydroxy-2-methylphenoxy)-2-methylpropanoateHCID 21935754[2-Methyl-6-(4-trifluoromethoxy-phenyl)-4-trifluoromethyl-pyridin-3-yl]-methanol

Product 1

HCID 865978142-Methyl-2-{2-methyl-4-[2-methyl-6-(4-trifluoromethoxy-phenyl)-4-trifluoromethyl-pyridin-3-ylmethoxy]-phenoxy}-propionic acid ethyl esterYield 75%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To an ice cold solution of 2-(4-hydroxy-2-methyl-phenoxy)-2-methyl-propionic acid ethyl ester (35 mg, 147 μmol; described in WO 02/092590), [2-methyl-6-(4-trifluoromethoxy-phenyl)-4-trifluoromethyl-pyridin-3-yl]-methanol (52 mg, 148 μmol, example 112E]) and tributylphosphine (50 μl, 178 μmol) in tetrahydrofuran (3.5 ml) was added N,N,N′,N′-tetramethyl azodicarboxamide (30 mg, 178 mmol). The cooling bath was removed and stirring continued for 14 h. The mixture was filtered over celite and the solvent removed under reduced pressure to give a yellow oil which was purified by column chromatography (silica gel, heptane/AcOEt) to give 63 mg (110 μmol, 75%) of the title compound as colorless oil.

Workup

  1. customThe cooling bath was removed
  2. filtrationThe mixture was filtered over celite
  3. customthe solvent removed under reduced pressure
  4. customto give a yellow oil which
  5. customwas purified by column chromatography (silica gel, heptane/AcOEt)

Sources & evidence

ORD record
ord-fb4a1603807c4009bba1b35028aec964
Source dataset
uspto-grants-2006_10
Patent number
US07115611B2

Reaction notes

Loading…