2-(Trifluoromethyl)oxirane → Methyl 3-(((3-phenoxyphenyl)(3,3,3-trifluoro-2-hydroxypropyl)amino)methyl)benzoate

HRID 1017014Notes

Reaction equation

HRID 1017014 reaction equation
[O:1]([C:8]1[CH:9]=[C:10]([NH:14][CH2:15][C:16]2[CH:17]=[C:18]([CH:23]=[CH:24][CH:25]=2)[C:19]([O:21][CH3:22])=[O:20])[CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:26][C:27]([F:32])([F:31])[CH:28]1[O:30][CH2:29]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.O.C(Cl)Cl>[O:1]([C:8]1[CH:9]=[C:10]([N:14]([CH2:15][C:16]2[CH:17]=[C:18]([CH:23]=[CH:24][CH:25]=2)[C:19]([O:21][CH3:22])=[O:20])[CH2:29][CH:28]([OH:30])[C:27]([F:32])([F:31])[F:26])[CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 3

HCID 5207692-(Trifluoromethyl)oxiraneHCID 2733225Ytterbium triflateHCID 23506109Methyl 3-[[(3-phenoxyphenyl)amino]methyl]benzoate

Product 1

HCID 10993963Methyl 3-(((3-phenoxyphenyl)(3,3,3-trifluoro-2-hydroxypropyl)amino)methyl)benzoateYield 96%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
50 °C

Procedure

EX-612B) To a mixture of methyl 3-[[(3-phenoxyphenyl)amino]methyl]benzoate (6.2 g, 0.019 mol) from EX-612A and 1,1,1-trifluoro-2,3-epoxypropane (8.58 g, 0.077 mol) in 12 mL of acetonitrile was added ytterbium (III) trifluoromethanesulfonate (1.2 g, 0.0019 mol). The resulting mixture was heated at 50° C. in a sealed glass tube for 18 h. The reaction mixture was cooled to room temperature, then diluted with water and methylene chloride. The aqueous layer was extracted with methylene chloride. The organic layers were combined, dried over MgSO4, and concentrated in vacuo. The crude product was purified by column chromatography on silica gel eluting with 1:9-ethyl acetate in hexane to afford 8.0 g (96%) of the desired methyl 3-[[(3-phenoxy-phenyl)(3,3,3-trifluoro-2-hydroxypropyl)amino]methyl]benzoate product as a yellow oil. Anal. calcd. for C24R22F3NO4.1.4 H2O: C, 61.25; H. 5.31; N, 2.98.found: C. 61.52; H, 5.06; N, 2.89.HRMS calcd.: 446.1579 [M+H]+, found: 446.1596. 1H NMR (CDCl3) δ7.28 (m, 4H), 7.14 (t, 1H), 7.07, (m, 3H), 7.00 (s, 1H), 6.94 (d, 2H), 6.46 (dd, 1H), 6.38 (dd, 1H), 6.35 (t, 1H), 5.84 (t, 1H), 4.60 (t. 2H), 4.36 (m, 1H), 3.82 (d, 1H), 3.48 (m, 1H), 2.51 (s, 1H). 19F NMR (CDCl3) δ−79.0 (d, 3F).

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionThe aqueous layer was extracted with methylene chloride
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by column chromatography on silica gel eluting with 1

Sources & evidence

ORD record
ord-58a7b16682544bf88afb5876b79766b2
Source dataset
uspto-grants-2002_11
Patent number
US06476057B1

Reaction notes

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