Lithium hydroxide, monohydrate → 2-(2-(2-((2R,5S)-4-(4-fluorobenzyl)-2,5-dimethylpiperazin-1-yl)-2-oxoethoxy)-5-chlorophenyl)acetic acid

HRID 11653Notes

Reaction equation

HRID 11653 reaction equation
C([O:3][C:4](=[O:33])[CH2:5][C:6]1[CH:11]=[C:10]([Cl:12])[CH:9]=[CH:8][C:7]=1[O:13][CH2:14][C:15]([N:17]1[CH2:22][C@H:21]([CH3:23])[N:20]([CH2:24][C:25]2[CH:30]=[CH:29][C:28]([F:31])=[CH:27][CH:26]=2)[CH2:19][C@H:18]1[CH3:32])=[O:16])C.O.[OH-].[Li+]>O1CCCC1.CO.O>[Cl:12][C:10]1[CH:9]=[CH:8][C:7]([O:13][CH2:14][C:15]([N:17]2[CH2:22][C@H:21]([CH3:23])[N:20]([CH2:24][C:25]3[CH:26]=[CH:27][C:28]([F:31])=[CH:29][CH:30]=3)[CH2:19][C@H:18]2[CH3:32])=[O:16])=[C:6]([CH2:5][C:4]([OH:33])=[O:3])[CH:11]=1

Participants

6

Reactant 2

HCID 168937Lithium hydroxide, monohydrateHCID 44431526(5-Chloro-2-{2-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-oxo-ethoxy}-phenyl)-acetic Acid Ethyl Ester

Product 1

HCID 444315272-(2-(2-((2R,5S)-4-(4-fluorobenzyl)-2,5-dimethylpiperazin-1-yl)-2-oxoethoxy)-5-chlorophenyl)acetic acidYield 81.8%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of (5-chloro-2-{2-[4-(4-fluoro-benzyl)-(2R,5S)-2,5-dimethyl-piperazin-1-yl]-2-oxo-ethoxy}-phenyl)-acetic acid ethyl ester (5.1 g, 10.7 mmol) in tetrahydrofuran (30 mL), methanol (30 mL) and water (6 mL) was added lithium hydroxide monohydrate (2.2 g, 53.5 mmol). The reaction was stirred for 18 hour at ambient temperature. The reaction was then concentrated in vacuo and the remaining solution was acidified with a 1M aqueous hydrochloric acid and extracted with dichloromethane. The organic layer was dried over magnesium sulfate, filtered and concentrated in vacuo. The crude product was diluted with minimal dichloromethane and diethyl ether was added. A white precipitate was collected by filtration to give the title compound (3.93 g).

Workup

  1. concentrationThe reaction was then concentrated in vacuo
  2. extractionextracted with dichloromethane
  3. dry with materialThe organic layer was dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. additionThe crude product was diluted with minimal dichloromethane and diethyl ether
  7. additionwas added
  8. filtrationA white precipitate was collected by filtration

Sources & evidence

ORD record
ord-cbd2f8a497854c03862d29da73f2aceb
Source dataset
uspto-grants-2006_08
Patent number
US07098212B2

Reaction notes

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