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

HRID 990459Notes

Reaction equation

HRID 990459 reaction equation
[N+:1]([C:4]1[CH:5]=[C:6]([NH:10][CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([O:18][C:19]([F:24])([F:23])[CH:20]([F:22])[F:21])[CH:13]=2)[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2].[F:25][C:26]([F:31])([F:30])[CH:27]1[O:29][CH2:28]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>[N+:1]([C:4]1[CH:5]=[C:6]([N:10]([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([O:18][C:19]([F:23])([F:24])[CH:20]([F:21])[F:22])[CH:13]=2)[CH2:28][CH:27]([OH:29])[C:26]([F:31])([F:30])[F:25])[CH:7]=[CH:8][CH:9]=1)([O-:3])=[O:2]

Participants

5

Reactant 3

HCID 5207692-(Trifluoromethyl)oxiraneHCID 2733225Ytterbium triflateHCID 23506093N-(3-nitrophenyl)-3-(1,1,2,2-tetrafluoroethoxy)benzenemethanamine

Product 1

HCID 235060533-[(3-Nitrophenyl)[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]amino]1,1,1-trifluoro-2-propanolYield 45%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Conditions

Temperature
55 °C

Procedure

EX-528B) N-(3-nitrophenyl)-3-(1,1,2,2-tetrafluoroethoxy)benzene-methanamine (3.25 g, 9.44 mmol) from EX-528A and 1,1,1-trifluoro-2,3-epoxypropane (0.895 mL, 10.4 mmol) were dissolved in 15 mL of acetonitrile. Ytterbium (III) trifluoromethane-sulfonate (0.77 g, 1.24 mmol) was added, and the stirred solution was warmed to 55° C. for 48 hours. The reaction was quenched with water and extracted with ethyl acetate. The organic layer was dried over MgSO4, and concentrated in vacuo. The crude product was purified by flash column chromatography on silica gel eluting with ethyl acetate:hexane 1:10 to give 1.93 g (45%) of the desired 3-[(3-nitrophenyl)[[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol product as a brown oil. HRMS calcd. for C18H16F7N2O4: 457.0998 [M+H]+, found: 457.1008. 1H NMR (CDCl3) δ 3.7 (dd, 1H), 3.9 (dd, 1H), 4.4 (m, 1H), 4.8 (m, 2H), 5.9 (tt, 1H), 7.0-7.2 (m, 4H), 7.3-7.4 (m, 2H), 7.6 (m, 2H).

Workup

  1. customThe reaction was quenched with water
  2. extractionextracted with ethyl acetate
  3. dry with materialThe organic layer was dried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe crude product was purified by flash column chromatography on silica gel eluting with ethyl acetate:hexane 1:10

Sources & evidence

ORD record
ord-75b9115712e5436f9769cd42777628a5
Source dataset
uspto-grants-2002_10
Patent number
US06458849B1

Reaction notes

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