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

HRID 852391Notes

Reaction equation

HRID 852391 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]O.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:68])[C:53]([O:56][C:57]1[CH:62]=[CH:61][C:60]([S:63]C(=O)C)=[CH:59][C:58]=1[CH3:67])([CH3:55])[CH3:54])[CH3:50].C([O-])([O-])=O.[Cs+].[Cs+]>C(Cl)Cl.C(#N)C.CO>[CH2:49]([O:51][C:52](=[O:68])[C:53]([O:56][C:57]1[CH:62]=[CH:61][C:60]([S:63][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:18])([F:17])[F:16])=[CH:10][CH:9]=2)=[CH:59][C:58]=1[CH3:67])([CH3:54])[CH3:55])[CH3:50]

Participants

9

Reactant 5

HCID 10796Cesium carbonateHCID 67749Trifluoromethanesulfonic anhydrideHCID 685102,6-Di-tert-butylpyridineHCID 688212542,2-Dimethyl-5-(4-trifluoromethoxy-phenyl)-pent-4-yn-1-olHCID 865978202-(4-Acetylsulfanyl-2-methyl-phenoxy)-2-methyl-propionic acid ethyl ester

Product 1

HCID 694576962-{4-[2,2-Dimethyl-5-(4-trifluoromethoxy-phenyl)-pent-4-ynylsulfanyl]-2-methyl-phenoxy}-2-methyl-propionic acid ethyl esterYield 88.5%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

A solution of 0.109 g (0.40 mmol) 2,2-dimethyl-5-(4-trifluoromethoxy-phenyl)-pent-4-yn-1-ol (example 24E]) in 0.4 ml CH2Cl2 was treated at 0° C. with 0.11 ml (0.48 mmol) 2,6-di-tert-butylpyridine and 0.07 ml (0.44 mmol) trifluoromethanesulfonic anhydride. After 1.5 h at 0° C. the solution was evaporated, dissolved in 1.5 ml acetonitrile and added to a suspension of 0.142 g (0.48 mmol) of 2-(4-acetylsulfanyl-2-methyl-phenoxy)-2-methyl-propionic acid ethyl ester (example 1C]) and 0.274 g (0.84 mmol) of Cs2CO3 in 2.5 ml of acetonitrile and 0.1 ml of MeOH. After vigorous stirring for 20 h at ambient temperature and filtration, the solvent was evaporated and the residue re-dissolved in dichloromethane and filtered again and evaporated. Purification by flash chromatography (SiO2, n-heptane/EtOAc 2.5%) yielded 0.18 g of the title compound as colorless viscous oil.

Workup

  1. customAfter 1.5 h at 0° C. the solution was evaporated
  2. dissolutiondissolved in 1.5 ml acetonitrile
  3. filtrationfiltration
  4. customthe solvent was evaporated
  5. dissolutionthe residue re-dissolved in dichloromethane
  6. filtrationfiltered again
  7. customevaporated
  8. customPurification by flash chromatography (SiO2, n-heptane/EtOAc 2.5%)

Sources & evidence

ORD record
ord-c326099b242340f29c7da49be92d64f3
Source dataset
uspto-grants-2007_08
Patent number
US07253192B2

Reaction notes

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