Ethanol → 3-((3-(1,1,2,2-Tetrafluoroethoxy)benzyl)(3-(4-aminophenoxy)phenyl)amino)-1,1,1-trifluoropropan-2-ol

HRID 990407Notes

Reaction equation

HRID 990407 reaction equation
[N+:1]([C:4]1[CH:38]=[CH:37][C:7]([O:8][C:9]2[CH:10]=[C:11]([N:15]([CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([O:30][C:31]([F:36])([F:35])[CH:32]([F:34])[F:33])[CH:25]=3)[CH2:16][CH:17]([OH:22])[C:18]([F:21])([F:20])[F:19])[CH:12]=[CH:13][CH:14]=2)=[CH:6][CH:5]=1)([O-])=O.[H][H].[CH2:41](O)[CH3:42]>[Pd]>[NH2:1][C:4]1[CH:5]=[CH:6][C:7]([O:8][C:9]2[CH:10]=[C:11]([N:15]([CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([O:30][C:31]([F:35])([F:36])[CH:32]([F:33])[F:34])[CH:25]=3)[CH2:16][CH:17]([OH:22])[C:18]([F:21])([F:20])[F:19])[CH:12]=[CH:13][CH:14]=2)=[CH:37][CH:38]=1.[CH2:41]([NH:1][C:4]1[CH:38]=[CH:37][C:7]([O:8][C:9]2[CH:10]=[C:11]([N:15]([CH2:23][C:24]3[CH:29]=[CH:28][CH:27]=[C:26]([O:30][C:31]([F:36])([F:35])[CH:32]([F:34])[F:33])[CH:25]=3)[CH2:16][CH:17]([OH:22])[C:18]([F:21])([F:20])[F:19])[CH:12]=[CH:13][CH:14]=2)=[CH:6][CH:5]=1)[CH3:42]

Participants

6

Reactant 3

HCID 702EthanolHCID 111244671,1,1-Trifluoro-3-((3-(4-nitrophenoxy)phenyl)(3-(1,1,2,2-tetrafluoroethoxy)benzyl)amino)propan-2-olHCID 178418361HCID 178418361, compound

Product 2

HCID 110818833-((3-(1,1,2,2-Tetrafluoroethoxy)benzyl)(3-(4-aminophenoxy)phenyl)amino)-1,1,1-trifluoropropan-2-olHCID 235060983-[[3-(4-(Ethylamino)phenoxy]phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol

Reagents, catalysts & solvents 1

HCID 23938PalladiumCatalyst

Procedure

A solution of 3-[[3-(4-nitrophenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy) phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol (33.8 mg, 0.06 mmol) in ethanol and 5% palladium on carbon (4 mL) was placed under 40 psi hydrogen gas for 7H. The mixture was filtered through celite, the solvent was evaporated, and the residue was purified by silica gel chromatography eluting with 25% ethyl acetate in hexane to give 13.4 mg (42%) of (EX-450A) as 3-[[3(4-aminophenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy) phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol and 13.9 mg (41%) of (EX-450B) as 3-[[3-[4-(ethylamino)phenoxy]phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]amino]-1,1,1-trifluoro-2-propanol both as orange oils. 3-[[3-(4-aminophenoxy)phenyl][[3-(1,1,2,2-tetrafluoroethoxy)phenyl]methyl]-amino]-1,1,1-trifluoro-2-propanol: HRMS calcd. for C24H22F7N2)3: 519.1519 [M+H]+, found: 519.1529. 1H NMR (acetone-d6) δ3.63 (dd, 1H), 3.96 (dd, 1H), 4.42-4.58 (m, 1H), 4.80 (s, 2H), 5.88 (m, 1H), 6.20 (m, 1H), 6.32-6.77 (m, 6H), 6.92 (d, 1H), 7.06-7.26 (m, 3H), 7.43 (m, 1H). 3-[[3-[4-(ethylamino)phenoxyphenyl][[3-(1,1,2,2-tetrafluoroethoxy) phenyl]-methyl]amino]-1,1,1-trifluoro-2-propanol: HRMS calcd. for C26H26F7N2O3: 547.1832 [M+H]+. found: 547.1819. 1H NMR (acetone-d6) δ1.23 (t, 3H), 3.17 (q, 2H), 3.63 (dd, 1H), 3.96 (dd, 1H), 4.424.58 (m, 1H), 4.79 (s, 2H), 5.85 (d, 1H), 6.20 (m, 1H), 6.33 (m, 1H), 6.47 (m, 1H), 6.50 (tt, 1J), 6.61 (d, 2H), 6.78 (d, 2H), 7.09 (t, 1H), 7.20 (m, 1H), 7.23 (d, 1H), 7.42 (m, 1H).

Workup

  1. filtrationThe mixture was filtered through celite
  2. customthe solvent was evaporated
  3. customthe residue was purified by silica gel chromatography
  4. washeluting with 25% ethyl acetate in hexane

Sources & evidence

ORD record
ord-3bdc39b8c35748f986ed396b4224efea
Source dataset
uspto-grants-2002_10
Patent number
US06458803B1

Reaction notes

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