2-(Trifluoromethyl)oxirane → 3-((3-Tert-butoxybenzyl)(3-phenoxyphenyl)amino)-1,1,1-trifluoropropan-2-ol

HRID 1840110Notes

Reaction equation

HRID 1840110 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]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])[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:27][C:28]([F:33])([F:32])[CH:29]1[O:31][CH2:30]1>C(#N)C.[O-]S(C(F)(F)F)(=O)=O.[Yb+3].[O-]S(C(F)(F)F)(=O)=O.[O-]S(C(F)(F)F)(=O)=O>[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][C:23]([CH3:26])([CH3:25])[CH3:24])[CH:17]=2)[CH2:30][CH:29]([OH:31])[C:28]([F:33])([F:32])[F:27])[CH:11]=[CH:12][CH:13]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 5207692-(Trifluoromethyl)oxirane2×HCID 10936948N-(3-phenoxyphenyl)[[3-(1,1-dimethylethoxy)phenyl]methyl]amine

Product 1

HCID 117332173-((3-Tert-butoxybenzyl)(3-phenoxyphenyl)amino)-1,1,1-trifluoropropan-2-olYield 42%

Reagents, catalysts & solvents 2

HCID 2733225Ytterbium triflateCatalystHCID 6342AcetonitrileSolvent2×

Conditions

Temperature
45 °C

Procedure

The N-(3-phenoxyphenyl)[[3-(1,1-dimethylethoxy)phenyl]methyl]amine (0.270 g, 0.78 mmol) product from EX-654B was dissolved in 2 mL of acetonitrile. Ytterbium triflate (16 mg, 0.026 mmol) was added in 0.5 mL of acetonitrile, and the mixture was stiffed under nitrogen. 1,1,1-Trifluoro-2,3-epoxypropane (0.105 g, 0.94 mmol) was added, the vial was sealed and heated to 45° C. After 24 h, TLC analysis showed 50% conversion, so additional 1,1,1-trifluoro-2,3-epoxypropane (88.6 mg, 0.79 mmol) was added and heating continued for an additional 24 h. The resulting mixture was eluted from silica gel with an ethyl acetate in hexane gradient (1.5-7% ethyl acetate). Fractions were pooled based on TLC analysis to give 150 mg (42%) of the desired 3-[(3-phenoxy-phenyl)[[3-(1, 1-dimethylethoxy)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol product as a clear, colorless oil, and an additional 60 mg (17%) was obtained as an amber oil. HRMS calcd. for C26H28F3NO3: 460.2100 [M+H]+, found: 460.2103. 1H NMR (C6D6) δ 6.78-7.08 (m, 9H), 6.68 (d, 1H), 6.55 (t, 1H), 6.43 (dd, 1H), 6.34 (dd, 1H), 4.23 (s, 2H), 3.81 (m, 1H), 3.48 (dd, 1H), 3.24 (m, 1H), 2.25 (br s, 1H), 1.07 (s, 9H). 19F NMR (C6D6) δ −78.92 (d, 3F).

Workup

  1. customthe vial was sealed
  2. additionwas added
  3. temperatureheating
  4. waitcontinued for an additional 24 h
  5. washThe resulting mixture was eluted from silica gel with an ethyl acetate in hexane gradient (1.5-7% ethyl acetate)

Sources & evidence

ORD record
ord-ac7bb7b702b94f8aa1c9095214856d53
Source dataset
uspto-grants-2004_01
Patent number
US06677353B2

Reaction notes

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