Lithium Hydroxide → 3-Cyclopentyl-2-(4-pyridin-2-ylethynyl-phenyl)-propionic acid

HRID 1936264Notes

Reaction equation

HRID 1936264 reaction equation
C[O:2][C:3](=[O:25])[CH:4]([C:11]1[CH:16]=[CH:15][C:14]([C:17]#[C:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=2)=[CH:13][CH:12]=1)[CH2:5][CH:6]1[CH2:10][CH2:9][CH2:8][CH2:7]1.[OH-].[Li+]>CO.O.O1CCCC1>[CH:6]1([CH2:5][CH:4]([C:11]2[CH:12]=[CH:13][C:14]([C:17]#[C:18][C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][N:20]=3)=[CH:15][CH:16]=2)[C:3]([OH:25])=[O:2])[CH2:10][CH2:9][CH2:8][CH2:7]1

Participants

6

Reactant 2

HCID 3939Lithium Hydroxide2×HCID 674839823-Cyclopentyl-2-(4-pyridin-2-ylethynyl-phenyl)-propionic acid methyl ester

Product 1

HCID 674844363-Cyclopentyl-2-(4-pyridin-2-ylethynyl-phenyl)-propionic acidYield 98%

Reagents, catalysts & solvents 3

HCID 887MethanolSolventHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
25 °C

Procedure

A solution of 3-cyclopentyl-2-(4-pyridin-2-ylethynyl-phenyl)-propionic acid methyl ester (930 mg, 2.79 mmol) in methanol (5 mL), water (2 mL) and tetrahydrofuran (1 mL) was treated with lithium hydroxide (80 mg, 1.90 mmol). The reaction mixture was stirred at 25° C. for 60 h. At this time, additional lithium hydroxide (100 mg, 2.38 mmol) was added. The reaction was stirred at 25° C. for 3 h. At this time, the reaction was diluted with water (10 mL) and then concentrated in vacuo. The resulting aqueous layer was washed with ethyl acetate (2×10 mL), acidified with a 1N aqueous hydrochloric acid solution, and then extracted with ethyl acetate (2×25 mL). The combined organic extracts were dried over magnesium sulfate, filtered and concentrated in vacuo to afford 3-cyclopentyl-2-(4-pyridin-2-ylethynyl-phenyl)-propionic acid (873 mg, 98%) as an amber solid: mp 143-147° C.; EI-HRMS m/e calcd for C21H21NO2 (M+) 319.1572, found 319.1580.

Workup

  1. stirringThe reaction was stirred at 25° C. for 3 h
  2. concentrationconcentrated in vacuo
  3. washThe resulting aqueous layer was washed with ethyl acetate (2×10 mL)
  4. extractionextracted with ethyl acetate (2×25 mL)
  5. dry with materialThe combined organic extracts were dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-0e1bf15b4863440cb38828e7744f745a
Source dataset
uspto-grants-2002_05
Patent number
US06388071B2

Reaction notes

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