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

HRID 1261507Notes

Reaction equation

HRID 1261507 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][CH2:6][S:7][CH3:8].O.[OH-].[Li+]>O1CCCC1.O>[CH3:8][S:7][CH2:6][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:20])([F:21])[F:19])[C:10]1=[O:22])[C:3]([OH:23])=[O:2]

Participants

4

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 70945579(S)-4-methylsulfanyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-butyric acid methyl ester

Product 1

HCID 70944912(S)-4-methylsulfanyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-butyric acidYield 97%

Reagents, catalysts & solvents 1

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

Procedure

A solution of (S)-4-methylsulfanyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-butyric acid methyl ester (134 mg, 0.39 mmol) in tetrahydrofuran/water (6 mL, 1:1) was treated with lithium hydroxide monohydrate (33 mg, 0.78 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 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-methylsulfanyl-2-(1-oxo-4-trifluoromethyl-1,3-dihydro-isoindol-2-yl)-butyric acid (126 mg, 97%) as a white foam: HR-ES(+) m/e calcd for C14H14NO3SF3 [M+H]+ 334.0719, observed 334.0717; 1H NMR (400 MHz, CHLOROFORM-d) δ 8.07 (d, J=7.46 Hz, 1H), 7.83 (d, J=7.67 Hz, 1H), 7.59-7.71 (m, 1H), 5.25 (dd, J=4.48, 10.44 Hz, 1H), 4.79 (d, J=17.47 Hz, 1H), 4.56 (d, J=17.47 Hz, 1H), 2.41-2.66 (m, 3H), 2.20-2.35 (m, 1H), 2.13 (s, 3H).

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
  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-13c81749110b4cc88c294508039d5101
Source dataset
uspto-grants-2013_06
Patent number
US08470866B2

Reaction notes

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