2-(Trifluoromethyl)oxirane → 3-[(3-Phenoxyphenyl)[[3-(2-hydroxy-3,3,3-trifluoro-n-propoxy)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol

HRID 990554Notes

Reaction equation

HRID 990554 reaction equation
[O:1]([C:8]1[CH:9]=[C:10]([NH:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([OH:22])[CH:17]=2)[CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:23][C:24]([F:29])([F:28])[CH:25]1[O:27][CH2:26]1>>[O:1]([C:8]1[CH:9]=[C:10]([N:14]([CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[C:18]([O:22][CH2:26][CH:25]([OH:27])[C:24]([F:29])([F:28])[F:23])[CH:17]=2)[CH2:26][CH:25]([OH:27])[C:24]([F:29])([F:28])[F:23])[CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

3

Reactant 2

HCID 5207692-(Trifluoromethyl)oxirane2×HCID 109462273-[[(3-Phenoxyphenyl)amino]methyl]phenol

Product 1

HCID 110385763-[(3-Phenoxyphenyl)[[3-(2-hydroxy-3,3,3-trifluoro-n-propoxy)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanolYield 77%

Conditions

Temperature
95 °C

Procedure

The N-(3-phenoxyphenyl)[[3-hydroxyphenyl]methyl]amine (400 mg, 1.35 mmol) product from EX-655A and 1,1,1-trifluoro-2,3-epoxypropane (348 mg, 3 mmol) were placed in a sealed vial, then stirred and heated to 95° C. for 15 h under an atmosphere of nitrogen. The vial was cooled, and more 1,1,1-trifluoro-2,3-epoxypropane (112 mg, 1 mmol) was added. The vial was sealed, then stirred and heated to 95° C. for a further 20 h under an atmosphere of nitrogen. The crude product was purified by flash column chromatography on silica gel eluting with ethyl acetate in hexane (1:6) to give 518 mg (77%) of the desired 3-[(3-phenoxyphenyl)[[3-(2-hydroxy-3,3,3-trifluoro-n-propoxy)-phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol product as a light amber oil, 98% pure by HPLC analysis. 1H NMR (CDCl3) δ7.20-7.32 (m, 3H), 7.14 (t, 1H), 7.07 (t, 1H), 6.95 (d, 2H), 6.80 (m, 2H), 6.74 (s, 1H), 6.48 (dd, 1H), 6.38 (m, 2H), 4.59 (ABq, 2H), 4.31 (m, 1 H), 4.18 (dd, 1 H), 4.10 (dd, 1H), 3.83 (dd, 1H), 3.54 (dd, 1H), 2.92 (d, 1H), 2.61 (d, 1H). 1919F NMR (CDCl3) δ−78.0 (d, 3F), −79.2 (d, 3F). HRMS calcd. for C25H23F6 NO4: 516.1611 [M+H]+, found: 516.1618.

Workup

  1. temperatureThe vial was cooled
  2. customThe vial was sealed
  3. stirringstirred
  4. temperatureheated to 95° C. for a further 20 h under an atmosphere of nitrogen
  5. customThe crude product was purified by flash column chromatography on silica gel eluting with ethyl acetate in hexane (1:6)

Sources & evidence

ORD record
ord-01498111700c4770867354cbddf1f815
Source dataset
uspto-grants-2002_10
Patent number
US06458852B1

Reaction notes

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