Hydrochloric Acid → HCID 2050653, compound

HRID 2066166Notes

Reaction equation

HRID 2066166 reaction equation
C([O:3][C:4](=[O:20])[CH2:5][N:6]1[CH2:11][CH2:10][N:9]([C:12](=[O:19])[C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[CH2:8][CH2:7]1)C.CO.[OH-].[Li+].Cl>O>[C:12]([N:9]1[CH2:8][CH2:7][N:6]([CH2:5][C:4]([OH:20])=[O:3])[CH2:11][CH2:10]1)(=[O:19])[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=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

To (4-benzoylpiperazin-1-yl)acetic acid ethyl ester (8.19 g) were added methanol (300 ml) and water (50 ml), and lithium hydroxide (1.34 g) was added thereto in an ice water bath, followed by stirring for 10 min. The reaction mixture was allowed to warm up to room temperature and stirred for 24 hr. After addition of 1N hydrochloric acid (55.9 ml), the reaction mixture was concentrated under reduced pressure, and ethanol (200 ml) was added to the resultant residue. Precipitated insoluble matter was filtered through celite. The filtrate was concentrated to provide a crude product of (4-benzoylpiperazin-1-yl)acetic acid as a white solid (8.6 g). To (4-benzoylpiperazin-1-yl)acetic acid (2 g) was added N,N-dimethylformamide (80 ml) under a nitrogen atmosphere at room temperature, 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 thereto in this order, followed by stirring at room temperature for 66 hr. Liquid-liquid separation was carried out after addition of ethyl acetate (100 ml) and a saturated aqueous solution of sodium hydrogencarbonate (50 ml) to the reaction mixture. 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 solvent was removed under reduced pressure, and the resultant residue was purified by silica gel column chromatography (Fuji Silysia NH, eluent; ethyl acetate). Fractions containing the target compound were concentrated under reduced pressure, the resultant residue was suspended in diethyl ether (10 ml). The solid was collected by filtration, and dried under aeration to provide the titled compound as white powder (731.5 mg).

Workup

  1. additionwas added
  2. customin an ice water bath, followed
  3. stirringstirred for 24 hr
  4. concentrationthe reaction mixture was concentrated under reduced pressure, and ethanol (200 ml)
  5. additionwas added to the resultant residue
  6. filtrationPrecipitated insoluble matter was filtered through celite
  7. concentrationThe filtrate was concentrated

Sources & evidence

ORD record
ord-c7b75c10ba214da4b53c4e3ffaa31694
Source dataset
uspto-grants-2012_10
Patent number
US08288538B2

Reaction notes

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