2-(Trifluoromethyl)oxirane → 3-[[3-(4-Fluorophenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol

HRID 50503

Reaction equation

HRID 50503 reaction equation
[F:1][C:2]1[CH:29]=[CH:28][C:5]([O:6][C:7]2[CH:8]=[C:9]([NH:13][CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([O:21][C:22]([F:27])([F:26])[CH:23]([F:25])[F:24])[CH:16]=3)[CH:10]=[CH:11][CH:12]=2)=[CH:4][CH:3]=1.[F:30][C:31]([F:36])([F:35])[CH:32]1[O:34][CH2:33]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:3]=[CH:4][C:5]([O:6][C:7]2[CH:8]=[C:9]([N:13]([CH2:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([O:21][C:22]([F:26])([F:27])[CH:23]([F:24])[F:25])[CH:16]=3)[CH2:33][CH:32]([OH:34])[C:31]([F:36])([F:35])[F:30])[CH:10]=[CH:11][CH:12]=2)=[CH:28][CH:29]=1

Participants

5

Reactant 2

HCID 5207692-(Trifluoromethyl)oxiraneHCID 23505995N-[3-(4fluorophenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]amine

Product 1

HCID 102298083-[[3-(4-Fluorophenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanolYield 81%

Reagents, catalysts & solvents 2

HCID 2733225Ytterbium triflateCatalystHCID 6342AcetonitrileSolvent

Conditions

Temperature
40 °C

Procedure

The N-[3-(4-fluorophenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]amine (612 mg, 1.5 mmol) product from EX-634C and 1,1,1-trifluoro-2,3-epoxypropane (268 mg, 2.4 mmol) were dissolved in 1.0 mL of acetonitrile. Ytterbium (III) trifluoromethanesulfonate (43 mg, 0.07 mmol) was added, and the stirred solution was warmed to 40° C. for 2.5 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 brine and water, then dried over anhydrous MgSO4. The ether was removed in vacuo, and the crude product was purified by flash column chromatography on silica gel eluting with ethyl acetate in hexane (1:11) to give 633 mg (81%) of the desired 3-[[3-(4-fluorophenoxy)phenyl][[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. 1H NMR (CDCl3) δ 7.35 (t, 1H), 7.15 (m, 3H), 6.98 (m, 5H), 6.49 (dd, 1H), 6.38 (dd, 1H), 6.33 (m, 1H), 5.92 (tt, 1H), 4.67 (ABq, 2H), 4.37 (m, 1H), 3.91 (dd, 11H), 3.59 (dd, 1H), 2.48 (d, 1H). 19F NMR (CDCl3) δ −79.2 (d, 3F), −88.5 (m, 2F), −120.33 (m, 1F), −137.2 (dt, 2F). HRMS calcd. for C24H19F8NO3:522.1315 [M+H]+, found: 522.1297.

Workup

  1. customThe reaction was quenched with water
  2. extractionextracted with ether
  3. washThe ether layer was washed with brine and water
  4. dry with materialdried over anhydrous MgSO4
  5. customThe ether was removed in vacuo
  6. customthe crude product was purified by flash column chromatography on silica gel eluting with ethyl acetate in hexane (1:11)

Sources & evidence

ORD record
ord-052d860469244c009ad1a26f093997a3
Source dataset
uspto-grants-2004_03
Patent number
US06710089B2

Linked notes

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