Hydrochloric Acid → (S)-3-cyclohexyl-2-(4-fluoro-1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acid

HRID 2365734Notes

Reaction equation

HRID 2365734 reaction equation
C[O:2][C:3](=[O:23])[C@@H:4]([N:12]1[CH2:20][C:19]2[C:14](=[CH:15][CH:16]=[CH:17][C:18]=2[F:21])[C:13]1=[O:22])[CH2:5][CH:6]1[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]1.O.[OH-].[Li+].Cl>O1CCCC1.O>[CH:6]1([CH2:5][C@H:4]([N:12]2[CH2:20][C:19]3[C:14](=[CH:15][CH:16]=[CH:17][C:18]=3[F:21])[C:13]2=[O:22])[C:3]([OH:23])=[O:2])[CH2:11][CH2:10][CH2:9][CH2:8][CH2:7]1

Participants

6

Reactant 3

HCID 313Hydrochloric AcidHCID 168937Lithium hydroxide, monohydrateHCID 70945620(S)-3-cyclohexyl-2-(4-fluoro-1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acid methyl ester

Product 1

HCID 67484493(S)-3-cyclohexyl-2-(4-fluoro-1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acidYield 78%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

A mixture of (S)-3-cyclohexyl-2-(4-fluoro-1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acid methyl ester (311 mg, 0.97 mmol) in tetrahydrofuran (6 mL) at room temperature was treated with a mixture of lithium hydroxide monohydrate (82 mg, 1.95 mL) in water (6 mL). The reaction mixture was then stirred at room temperature until the reaction was complete by TLC (˜2 h). After this time, the reaction mixture was treated with 1N aqueous hydrochloric acid solution until the pH=2. The reaction mixture was then extracted with ethyl acetate (3×20 mL). The combined organic layers were then dried over magnesium sulfate, filtered to remove the drying agent and the filtrate was concentrated in vacuo to afford (S)-3-cyclohexyl-2-(4-fluoro-1-oxo-1,3-dihydro-isoindol-2-yl)-propionic acid (230 mg, 78%) as a white solid.

Workup

  1. customwas complete by TLC (˜2 h)
  2. extractionThe reaction mixture was then extracted with ethyl acetate (3×20 mL)
  3. dry with materialThe combined organic layers were then dried over magnesium sulfate
  4. filtrationfiltered
  5. customto remove the drying agent
  6. concentrationthe filtrate was concentrated in vacuo

Sources & evidence

ORD record
ord-e887b22554a54651b9d19a216ae33321
Source dataset
uspto-grants-2014_04
Patent number
US08697705B2

Reaction notes

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