Lithium Hydroxide → 2-{[4-(2-Oxo-2-{[4-(trifluoromethyl)benzyl]amino}ethyl)phenoxy]methyl}benzoic acid

HRID 2111971Notes

Reaction equation

HRID 2111971 reaction equation
[O:1]=[C:2]([NH:22][CH2:23][C:24]1[CH:29]=[CH:28][C:27]([C:30]([F:33])([F:32])[F:31])=[CH:26][CH:25]=1)[CH2:3][C:4]1[CH:21]=[CH:20][C:7]([O:8][CH2:9][C:10]2[CH:19]=[CH:18][CH:17]=[CH:16][C:11]=2[C:12]([O:14]C)=[O:13])=[CH:6][CH:5]=1.[OH-].[Li+]>C1COCC1.O>[O:1]=[C:2]([NH:22][CH2:23][C:24]1[CH:25]=[CH:26][C:27]([C:30]([F:31])([F:32])[F:33])=[CH:28][CH:29]=1)[CH2:3][C:4]1[CH:5]=[CH:6][C:7]([O:8][CH2:9][C:10]2[CH:19]=[CH:18][CH:17]=[CH:16][C:11]=2[C:12]([OH:14])=[O:13])=[CH:20][CH:21]=1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 68869576Methyl 2-{[4-(2-oxo-2-{[4-(trifluoromethyl)benzyl]amino}ethyl)phenoxy]methyl}-benzoate

Product 1

HCID 98246612-{[4-(2-Oxo-2-{[4-(trifluoromethyl)benzyl]amino}ethyl)phenoxy]methyl}benzoic acidYield 57%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

Methyl 2-{[4-(2-oxo-2-{[4-(trifluoromethyl)benzyl]amino}ethyl)phenoxy]methyl}-benzoate (71 mg, 0.155 mmol) in THF (1.5 ml) was cooled in an ice-bath. Lithium hydroxide (7.5 mg, 0.310 mmol) in water (1.5 ml) was dropped in. The cooling-bath was then removed and the mixture was stirred overnight. HPLC showed that the reaction was not complete. More lithium hydroxide (0.2M, 0.5 ml) was added. The reaction mixture was stirred for 4 days more. It was then evaporated in vacuum to remove THF. The residue was acidified with 1% hydrochloric acid, pH=3-4, and then extracted with ethyl acetate. The organic phase was dried with magnesium sulphate and evaporated. Chromatography of the residue on a column (ISOLUTE® SI, 2 g/6 ml) using DCM, MeOH/DCM (0.5:99.5, then 1:99, and then 2:98) as eluant gave 39 mg white solid product, yield 57%.

Workup

  1. customThe cooling-bath was then removed
  2. additionMore lithium hydroxide (0.2M, 0.5 ml) was added
  3. stirringThe reaction mixture was stirred for 4 days more
  4. customIt was then evaporated in vacuum
  5. customto remove THF
  6. extractionextracted with ethyl acetate
  7. dry with materialThe organic phase was dried with magnesium sulphate
  8. customevaporated

Sources & evidence

ORD record
ord-e2f3f06dab3e43ff81ad5f19304d604f
Source dataset
uspto-grants-2009_04
Patent number
US07521461B2

Reaction notes

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