2-(Trifluoromethyl)oxirane → 3-[(2,5-Difluorophenyl)[[3-(1,1,2,2-tetrafluoro-ethoxy)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol

HRID 1356774Notes

Reaction equation

HRID 1356774 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[NH:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([O:17][C:18]([F:23])([F:22])[CH:19]([F:21])[F:20])[CH:12]=1.[F:24][C:25]([F:30])([F:29])[CH:26]1[O:28][CH2:27]1>C(#N)C.FC(F)(F)S([O-])(=O)=O.[Yb+3].FC(F)(F)S([O-])(=O)=O.FC(F)(F)S([O-])(=O)=O>[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[N:9]([CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[C:13]([O:17][C:18]([F:22])([F:23])[CH:19]([F:20])[F:21])[CH:12]=1)[CH2:27][CH:26]([OH:28])[C:25]([F:30])([F:29])[F:24]

Participants

5

Reactant 2

HCID 5207692-(Trifluoromethyl)oxiraneHCID 11002165N-(2,5-difluorophenyl)[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]-methyl]amine

Product 1

HCID 235060713-[(2,5-Difluorophenyl)[[3-(1,1,2,2-tetrafluoro-ethoxy)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanolYield 84%

Reagents, catalysts & solvents 2

HCID 2733225Ytterbium triflateCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

EX-661B) The N-(2,5-difluorophenyl)[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]-amine (2.22 g, 6.67 mmol) product from EX-661A and 1,1,1-trifluoro-2,3-epoxypropane (1.12 g, 10 mmnol) were dissolved in 1.5 mL of acetonitrile. Ytterbium (III) trifluoromethanesulfonate (0.21 g, 0.33 mmol) was added, and the stirred solution was warmed to 50° C. for 2 h under an atmosphere of nitrogen, at which time HPLC analysis indicated that no secondary amine starting material remained. The reaction was quenched with water and extracted with ether. The ether layer was washed with water and brine, then dried over anhydrous MgSO4. The crude product was purified by flash column chromatography on silica gel eluting with ethyl acetate in hexane (1:10) to give 2.49 g (84%) of the desired 3-[(2,5-difluorophenyl)[[3-(1,1,2,2-tetrafluoro-ethoxy)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol product as a yellow oil, 99% pure by HPLC analysis. HRMS calcd. for C18H14FgNO2: 448.0959 [M+H]+, found: 448.0940.

Workup

  1. customThe reaction was quenched with water
  2. extractionextracted with ether
  3. washThe ether layer was washed with water and brine
  4. dry with materialdried over anhydrous MgSO4
  5. customThe crude product was purified by flash column chromatography on silica gel eluting with ethyl acetate in hexane (1:10)

Sources & evidence

ORD record
ord-ab4c3adb17354505ba877c579d61c53b
Source dataset
uspto-grants-2003_07
Patent number
US06586433B2

Reaction notes

Loading…