Water → HCID 11676374, compound

HRID 1173424Notes

Reaction equation

HRID 1173424 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]([CH2:23][C:24]([F:27])([F:26])[F:25])[CH2:10][CH2:11][O:12][C:13]2[CH:22]=[CH:21][C:16]([C:17]([O:19]C)=[O:18])=[CH:15][CH:14]=2)=[CH:5][C:4]=1[C:28]([F:31])([F:30])[F:29])#[N:2].O[Li].O.O>C1COCC1>[C:1]([C:3]1[CH:8]=[CH:7][C:6]([N:9]([CH2:23][C:24]([F:25])([F:26])[F:27])[CH2:10][CH2:11][O:12][C:13]2[CH:14]=[CH:15][C:16]([C:17]([OH:19])=[O:18])=[CH:21][CH:22]=2)=[CH:5][C:4]=1[C:28]([F:29])([F:30])[F:31])#[N:2]

Participants

5

Reactant 3

HCID 962WaterHCID 168937Lithium hydroxide, monohydrateHCID 11619223HCID 11619223, compound

Product 1

HCID 11676374HCID 11676374, compoundYield 97.8%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a solution of methyl 4-({2-[[4-cyano-3-(trifluoromethyl)phenyl](2,2,2-trifluoroethyl)amino]ethyl}oxy)benzoate (0.0863 g, 0.193 mmol, Example 32) in THF (3 mL) at rt was added LiOH.H2O (0.041 g, 0.97 mmol) and water (0.30 mL). The mixture was stirred 19 h at rt, then 8 h at reflux, cooled and partitioned between 1 N NaOH/Et2O. Layers were separated, and the aqueous layer extracted with Et2O (×1). The aqueous layer was then acidified to approximately pH 1 by addition of 2N HCl and extracted with EtOAc (×3). Combined EtOAc extracts were washed with brine, dried over Na2SO4 and concentrated in vacuo yielding 0.0816 g of the title compound as a colorless film which crystallized when triturated with CDCl3: 1H NMR (400 MHz, CD3OD) δ 7.97-7.90 (m, 2H), 7.75 (d, J=8.9 Hz, 1H), 7.38 (d, J=2.3 Hz, 1H), 7.28 (dd, J=8.9, 2.5 Hz, 1H), 6.97-6.92 (m, 2H), 4.45 (q, J=8.8 Hz, 2H), 4.31 (t, J=5.2 Hz, 2H), 4.08 (t, J=5.2 Hz, 2H); MS (ESI) m/z 431 (M−1).

Workup

  1. temperature8 h at reflux
  2. temperaturecooled
  3. custompartitioned between 1 N NaOH/Et2O
  4. customLayers were separated
  5. extractionthe aqueous layer extracted with Et2O (×1)
  6. additionThe aqueous layer was then acidified to approximately pH 1 by addition of 2N HCl
  7. extractionextracted with EtOAc (×3)
  8. washCombined EtOAc extracts were washed with brine
  9. dry with materialdried over Na2SO4
  10. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0c5aad408e264a6abdb8eff294422101
Source dataset
uspto-grants-2010_11
Patent number
US07834063B2

Reaction notes

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