Lithium hydroxide, monohydrate → (S)-4-methyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-pentanoic acid

HRID 2365745Notes

Reaction equation

HRID 2365745 reaction equation
C[O:2][C:3](=[O:23])[C@@H:4]([N:9]1[CH2:17][C:16]2[C:11](=[CH:12][CH:13]=[CH:14][C:15]=2[C:18]([F:21])([F:20])[F:19])[C:10]1=[O:22])[CH2:5][CH:6]([CH3:8])[CH3:7].O.[OH-].[Li+]>O1CCCC1.O>[CH3:7][CH:6]([CH3:8])[CH2:5][C@H:4]([N:9]1[CH2:17][C:16]2[C:11](=[CH:12][CH:13]=[CH:14][C:15]=2[C:18]([F:21])([F:19])[F:20])[C:10]1=[O:22])[C:3]([OH:23])=[O:2]

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 70944914(S)-4-methyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-pentanoic acid methyl ester

Product 1

HCID 70945056(S)-4-methyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-pentanoic acidYield 97.1%

Reagents, catalysts & solvents 1

HCID 21881883Oxolane--water (1/1)Solvent

Procedure

A solution of (S)-4-methyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-pentanoic acid methyl ester (274 mg, 0.83 mmol) in tetrahydrofuran/water (12 mL, 1:1) was treated with lithium hydroxide monohydrate (70 mg, 1.66 mmol) at room temperature. The reaction mixture was then stirred at room temperature for 2 h. After this time, the reaction mixture was concentrated in vacuo to remove the tetrahydrofuran. The resulting material was then diluted with a 1N aqueous hydrochloric acid solution (10 mL) and then extracted with ethyl acetate. The organic layers were combined and then dried over magnesium sulfate, filtered to remove the drying agent, and the filtrate was concentrated in vacuo to afford (S)-4-methyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-pentanoic acid (254 mg, 97%) as a white solid.

Workup

  1. concentrationAfter this time, the reaction mixture was concentrated in vacuo
  2. customto remove the tetrahydrofuran
  3. additionThe resulting material was then diluted with a 1N aqueous hydrochloric acid solution (10 mL)
  4. extractionextracted with ethyl acetate
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customto remove the drying agent
  8. concentrationthe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-792bf144adac4da7845538f1c8726693
Source dataset
uspto-grants-2014_04
Patent number
US08697705B2

Reaction notes

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