2-(Trifluoromethyl)oxirane → 3-[[[3-(1,1,2,2-Tetrafluoroethoxy)phenyl]methyl]-(3,3,3-trifluoro-2-hydroxypropyl)amino]benzonitrile

HRID 1016996Notes

Reaction equation

HRID 1016996 reaction equation
[F:1][C:2]([F:23])([O:6][C:7]1[CH:8]=[C:9]([CH2:13][NH:14][C:15]2[CH:16]=[C:17]([CH:20]=[CH:21][CH:22]=2)[C:18]#[N:19])[CH:10]=[CH:11][CH:12]=1)[CH:3]([F:5])[F:4].[F:24][C:25]([F:30])([F:29])[CH:26]1[O:28][CH2:27]1.FC(F)(F)S([O-])(=O)=O.[Yb+3].FC(F)(F)S([O-])(=O)=O.FC(F)(F)S([O-])(=O)=O>C(#N)C>[F:1][C:2]([F:23])([O:6][C:7]1[CH:8]=[C:9]([CH2:13][N:14]([CH2:27][CH:26]([OH:28])[C:25]([F:30])([F:29])[F:24])[C:15]2[CH:16]=[C:17]([CH:20]=[CH:21][CH:22]=2)[C:18]#[N:19])[CH:10]=[CH:11][CH:12]=1)[CH:3]([F:4])[F:5]

Participants

5

Reactant 3

HCID 5207692-(Trifluoromethyl)oxiraneHCID 2733225Ytterbium triflateHCID 235060273-[[[3-(1,1,2,2-Tetrafluoroethoxy)phenyl]methyl]amino]benzonitrile

Product 1

HCID 235060423-[[[3-(1,1,2,2-Tetrafluoroethoxy)phenyl]methyl]-(3,3,3-trifluoro-2-hydroxypropyl)amino]benzonitrileYield 76%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
50 °C

Procedure

The benzonitrile (1.58 g, 4.88 mmol) from EX-576A and 1,1,1-trifluoro-2,3-epoxy-propane (546 mL, 6.34 mmol) were dissolved in 4 mL of acetonitrile. Ytterbium (III) trifluoromethanesulfonate (304 mg, 0.49 mmol) was added, and the stirred solution was warmed to 50° C. overnight. The reaction was quenched with water and extracted with ether. The ether layer was washed with brine, dried over MgSO4 and evaporated. The crude product was purified by MPLC on silica gel eluting with dichloromethane to give 1.61 g (76%) of the desired 3-[[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]-(3,3,3-trifluoro-2-hydroxypropyl)amino]benzonitrile product as a clear oil, greater than 98% by reverse phase HPLC. HRMS calcd. for C19H15F7N2O2: 437.1100 [M+H]+, found: 437.1097. 1H NMR (CDCl3) δ3.60-3.69 (m, 1H), 3.86 (d, 1H), 4.32 (bs. 1H), 4.69 (q, 2H), 5.86 (dt, 1H), 6.85-6.95 (m, 2H), 6.97-7.01 (m, 2H), 7.04-7.12 (m, 2H), 7.23-7.37 (m, 2H).

Workup

  1. customThe reaction was quenched with water
  2. extractionextracted with ether
  3. washThe ether layer was washed with brine
  4. dry with materialdried over MgSO4
  5. customevaporated
  6. customThe crude product was purified by MPLC on silica gel eluting with dichloromethane

Sources & evidence

ORD record
ord-4ed34e93f9224afcafe491158f3ed54c
Source dataset
uspto-grants-2002_11
Patent number
US06476057B1

Reaction notes

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