Hydrochloric Acid → HCID 2050653, compound

HRID 1712639Notes

Reaction equation

HRID 1712639 reaction equation
CO.C([O:5][C:6](=[O:22])[CH2:7][N:8]1[CH2:13][CH2:12][N:11]([C:14](=[O:21])[C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)[CH2:10][CH2:9]1)C.[OH-].[Li+].Cl>O>[C:14]([N:11]1[CH2:10][CH2:9][N:8]([CH2:7][C:6]([OH:22])=[O:5])[CH2:13][CH2:12]1)(=[O:21])[C:15]1[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 887MethanolHCID 3939Lithium HydroxideHCID 46673126HCID 46673126, compound

Product 1

HCID 2050653HCID 2050653, compoundYield 116.9%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Methanol (300 ml) and water (50 ml) were added to (4-benzoylpiperazin-1-yl)acetic acid ethyl ester (8.19 g), and lithium hydroxide (1.34 g) was added thereto with cooling in an ice water bath, followed by stirring for 10 minutes. The reaction mixture was brought to room temperature, followed by stirring for 24 hours. After adding 1N hydrochloric acid (55.9 ml), the reaction mixture was concentrated under reduced pressure, and ethanol (200 ml) was added to the resultant residue. The precipitated insoluble matter was removed by filtration through celite. The filtrate was concentrated under reduced pressure to give a crude product of (4-benzoylpiperazin-1-yl)acetic acid (8.6 g) as a white solid. N,N-Dimethylformamide (80 ml) was added to (4-benzoylpiperazin-1-yl)acetic acid (2 g) at room temperature under a nitrogen atmosphere, and azetidine hydrochloride (1.51 g), triethylamine (4.49 ml), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide hydrochloride (3.09 g) and 1-hydroxybenzotriazole (2.18 g) were added in this order, followed by stirring at room temperature for 66 hours. Ethyl acetate (100 ml) and a saturated aqueous solution of sodium hydrogencarbonate (50 ml) were added to the reaction mixture, which was partitioned. The organic layer was washed with a saturated aqueous solution of sodium hydrogencarbonate (50 ml), water (50 ml) and brine (50 ml) in this order, and dried over anhydrous sodium sulfate. The residue obtained by distilling off the solvent under reduced pressure was purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate). The residue obtained by concentrating the fractions containing the target compound under reduced pressure was suspended by the addition of diethyl ether (10 ml). The solid was collected by filtration, and dried under aeration to give the title compound (731.5 mg) as white powder.

Workup

  1. additionwas added
  2. temperaturewith cooling in an ice water bath
  3. customwas brought to room temperature
  4. stirringby stirring for 24 hours
  5. concentrationthe reaction mixture was concentrated under reduced pressure, and ethanol (200 ml)
  6. additionwas added to the resultant residue
  7. customThe precipitated insoluble matter was removed by filtration through celite
  8. concentrationThe filtrate was concentrated under reduced pressure

Sources & evidence

ORD record
ord-85b193756ac7448db5add344b254d1ce
Source dataset
uspto-grants-2010_09
Patent number
US07790885B2

Reaction notes

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