Cesium carbonate → 2-{4-[2,2-Dimethyl-5-(4-trifluoromethoxy-phenyl)-pent-4-ynyloxy]-2-methyl-phenoxy}-2-methyl-propionic acid ethyl ester

HRID 852388Notes

Reaction equation

HRID 852388 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].C(C1C=CC=C(C(C)(C)C)N=1)(C)(C)C.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O.[CH2:49]([O:51][C:52](=[O:65])[C:53]([O:56][C:57]1[CH:62]=[CH:61][C:60](O)=[CH:59][C:58]=1[CH3:64])([CH3:55])[CH3:54])[CH3:50].C([O-])([O-])=O.[Cs+].[Cs+]>C(Cl)Cl.C(#N)C>[CH2:49]([O:51][C:52](=[O:65])[C:53]([O:56][C:57]1[CH:62]=[CH:61][C:60]([O:4][CH2:3][C:2]([CH3:19])([CH3:1])[CH2:5][C:6]#[C:7][C:8]2[CH:13]=[CH:12][C:11]([O:14][C:15]([F:16])([F:17])[F:18])=[CH:10][CH:9]=2)=[CH:59][C:58]=1[CH3:64])([CH3:54])[CH3:55])[CH3:50]

Participants

8

Reactant 5

HCID 10796Cesium carbonateHCID 67749Trifluoromethanesulfonic anhydrideHCID 685102,6-Di-tert-butylpyridineHCID 16756990Ethyl 2-(4-hydroxy-2-methylphenoxy)-2-methylpropanoateHCID 688212542,2-Dimethyl-5-(4-trifluoromethoxy-phenyl)-pent-4-yn-1-ol

Product 1

HCID 694584602-{4-[2,2-Dimethyl-5-(4-trifluoromethoxy-phenyl)-pent-4-ynyloxy]-2-methyl-phenoxy}-2-methyl-propionic acid ethyl esterYield 65%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 0.082 g (0.30 mmol) 2,2-dimethyl-5-(4-trifluoromethoxy-phenyl)-pent-4-yn-1-ol (example 24E]) in 0.3 ml CH2Cl2 was treated at 0° C. with 0.08 ml (0.36 mmol) 2,6-di-tert-butylpyridine and 0.05 ml (0.33 mmol) trifluoromethanesulfonic anhydride. After 2.5 h at 0° C. and 0.5 h at room temperature the solution was evaporated, dissolved in 1 ml acetonitrile and added to a solution of 0.071 g (0.30 mmol) 2-(4-hydroxy-2-methyl-phenoxy)-2-methyl-propionic acid ethyl ester (described in WO 02/092590) and 0.205 g (0.63 mmol) Cs2CO3 in 2 ml acetonitrile. The mixture was stirred for 20 h at room temperature and 1 h at reflux temperature. After filtration, the residue was dissolved in dichloromethane, dried (Na2SO4), filtered and evaporated. Purification by flash chromatography (SiO2, n-heptane/EtOAc 2%) yielded 0.096 g of the title compound as light yellow oil.

Workup

  1. custom0.5 h at room temperature the solution was evaporated
  2. dissolutiondissolved in 1 ml acetonitrile
  3. temperatureat reflux temperature
  4. filtrationAfter filtration
  5. dissolutionthe residue was dissolved in dichloromethane
  6. dry with materialdried (Na2SO4)
  7. filtrationfiltered
  8. customevaporated
  9. customPurification by flash chromatography (SiO2, n-heptane/EtOAc 2%)

Sources & evidence

ORD record
ord-6e664fe3155d4167837349dd1f198c3e
Source dataset
uspto-grants-2007_08
Patent number
US07253192B2

Reaction notes

Loading…