Lithium hydroxide, monohydrate → HCID 59403158, compound

HRID 1927782Notes

Reaction equation

HRID 1927782 reaction equation
[Cl:1][C:2]1[CH:35]=[CH:34][C:5]([CH2:6][CH2:7][NH:8][C:9]([C:11]2[CH:33]=[CH:32][C:14]([O:15][C:16]3[CH:21]=[CH:20][C:19]([CH2:22][C:23]([O:25]CC)=[O:24])=[CH:18][C:17]=3[C:28]([F:31])([F:30])[F:29])=[CH:13][CH:12]=2)=[O:10])=[CH:4][CH:3]=1.O[Li].O>CO.C1COCC1.O.C(OCC)(=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([CH2:6][CH2:7][NH:8][C:9]([C:11]2[CH:33]=[CH:32][C:14]([O:15][C:16]3[CH:21]=[CH:20][C:19]([CH2:22][C:23]([OH:25])=[O:24])=[CH:18][C:17]=3[C:28]([F:29])([F:30])[F:31])=[CH:13][CH:12]=2)=[O:10])=[CH:34][CH:35]=1

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 68468359HCID 68468359, compound

Product 1

HCID 59403158HCID 59403158, compoundYield 71.9%

Reagents, catalysts & solvents 3

HCID 962WaterCatalystHCID 8857Ethyl AcetateSolventHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

To a solution of ethyl 2-(4-(4-((4-chlorophenethyl)carbamoyl)phenoxy)-3-(trifluoromethyl)phenyl)acetate (0.165 g, 0.326 mmol) in methanol/THF (1:1), 5 ml was added LiOH—H2O (0.0684 g, 1.63 mmol) and 3 drops of water, and the reaction was stirred for 1 hour The reaction was diluted with ethyl acetate, washed with 2N HCl and brine, dried over magnesium sulfate and concentrated. The crude material was purified by silica gel chromatography, eluting with a gradient of 0.5% methanol/dichloromethane containing 0.5% AcOH to 7% methanol/dichloromethane containing 0.5% AcOH to provide 2-(4-(4-((4-chlorophenethyl) carbamoyl)phenoxy)-3-(trifluoromethyl)phenyl)acetic acid (0.112 g). MS+478.3 [M+1]. 1H NMR (400 MHz, CD3OD) δ 8.49 (bt, NH), 7.79 (d, J=8.7 Hz, 2H), 7.68 (s, 1H), 7.53 (d, J=4.3 Hz, 1H), 7.28 (d, J=8.5 Hz, 2H), 7.23 (d, J=8.6 Hz, 2H), 7.02-7.06 (m, 3H), 3.71 (s, 2H), 3.56 (t, J=6.8 Hz, 2H), 2.90 (t, J=7.3 Hz, 2H).

Workup

  1. washwashed with 2N HCl and brine
  2. dry with materialdried over magnesium sulfate
  3. concentrationconcentrated
  4. customThe crude material was purified by silica gel chromatography
  5. washeluting with a gradient of 0.5% methanol/dichloromethane containing 0.5% AcOH to 7% methanol/dichloromethane containing 0.5% AcOH

Sources & evidence

ORD record
ord-faa7dce8d1ca4b19832fa3a2774fd102
Source dataset
uspto-grants-2012_05
Patent number
US08183289B2

Reaction notes

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