Lithium Hydroxide → [3-(4-chlorophenyl)-5-oxo-4-(3,3,3-trifluoro-2-hydroxypropyl)-4,5-dihydro-1H-1,2,4-triazol-1-yl]-acetic acid

HRID 660902Notes

Reaction equation

HRID 660902 reaction equation
C[O:2][C:3](=[O:25])[CH2:4][N:5]1[C:9](=[O:10])[N:8]([CH2:11][CH:12]([OH:17])[C:13]([F:16])([F:15])[F:14])[C:7]([C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)=[N:6]1.[OH-].[Li+]>CO.O>[Cl:24][C:21]1[CH:22]=[CH:23][C:18]([C:7]2[N:8]([CH2:11][CH:12]([OH:17])[C:13]([F:16])([F:14])[F:15])[C:9](=[O:10])[N:5]([CH2:4][C:3]([OH:25])=[O:2])[N:6]=2)=[CH:19][CH:20]=1

Participants

5

Reactant 2

HCID 3939Lithium HydroxideHCID 58011736Methyl {3-(4-chlorophenyl)-5-oxo-4-(3,3,3-trifluoro-2-hydroxypropyl)-4,5-dihydro-1H-1,2,4-triazol-1-yl}acetate

Product 1

HCID 58011686[3-(4-chlorophenyl)-5-oxo-4-(3,3,3-trifluoro-2-hydroxypropyl)-4,5-dihydro-1H-1,2,4-triazol-1-yl]-acetic acid

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 962WaterSolvent

Procedure

The enantiomerically pure ester from Example 227A (265 mg, 0.70 mmol) is dissolved in 14 ml methanol and treated with 2.8 ml of a 1 M solution of lithium hydroxide in water. The mixture is stirred for 1 hr at RT and then freed of methanol on the rotary evaporator. The residue is diluted with 200 ml water and extracted once with dichloromethane. This organic phase is discarded. The aqueous phase is slowly acidified to pH 2 with 1 N hydrochloric acid. The product is extracted three times with dichloromethane, the combined organic phases are dried over sodium sulphate and the solvent removed on the rotary evaporator. The residue is dried under high vacuum. 142 mg (56% of theory) of the title compound are thus obtained. Since the aqueous phase still contains more product, it is evaporated to dryness on the rotary evaporator, and the residue is dissolved in a little DMSO and purified by preparative HPLC (Method 20). A further 71 mg (28% of theory) of the pure title compound are obtained.

Workup

  1. customfreed of methanol on the rotary evaporator
  2. additionThe residue is diluted with 200 ml water
  3. extractionextracted once with dichloromethane
  4. extractionThe product is extracted three times with dichloromethane
  5. dry with materialthe combined organic phases are dried over sodium sulphate
  6. customthe solvent removed on the rotary evaporator
  7. customThe residue is dried under high vacuum

Sources & evidence

ORD record
ord-3adc564136c24438a7bd801e421ddb0d
Source dataset
uspto-grants-2011_12
Patent number
US08084481B2

Reaction notes

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