Pyridine → 5-Benzyloxycarbonylamino-2-(4-{2-methoxyethyl}-3-oxopiperazin-1-yl)fluorobenzene

HRID 1108587Notes

Reaction equation

[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([N:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][O:17][CH3:18])[C:11](=[O:19])[CH2:10]2)=[C:6]([F:8])[CH:7]=1.N1C=CC=CC=1.Cl[C:27]([O:29][CH2:30][C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1)=[O:28]>ClCCl>[CH2:30]([O:29][C:27]([NH:1][C:2]1[CH:3]=[CH:4][C:5]([N:9]2[CH2:14][CH2:13][N:12]([CH2:15][CH2:16][O:17][CH3:18])[C:11](=[O:19])[CH2:10]2)=[C:6]([F:8])[CH:7]=1)=[O:28])[C:31]1[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=1

Participants

Conditions

Temperature: -20 °C

Procedure

5-Amino-2-(4-{2-methoxyethyl}-3-oxopiperazin-1-yl)fluorobenzene (3.5 g) was dissolved in dry dichloromethane (50 ml) under argon. Pyridine (1.33 ml) was added, and the mixture cooled to -20° C. Benzyl chloroformate (2.06 ml) was added, and the mixture stirred for 10 minutes at -20° C., before allowing the temperature to rise to ambient over 1.5 hours. Solvents were evaporated, the residue dissolved in dichloromethane and washed with sodium bicarbonate solution. After drying (MgSO4) and evaporation of solvent, the residue was chromatographed on silica, using as eluant a gradient increasing in polarity from 0 to 4% methanol in dichloromethane. Relevant fractions were combined and evaporated to give 5-benzyloxycarbonylamino-2-(4-{2-methoxyethyl}-3-oxopiperazin-1-yl)fluorobenzene (3.28 g).

Workup

waitto ambient over 1.5 hours
customSolvents were evaporated
dissolutionthe residue dissolved in dichloromethane
washwashed with sodium bicarbonate solution
customAfter drying
custom(MgSO4) and evaporation of solvent
customthe residue was chromatographed on silica
temperaturea gradient increasing in polarity from 0 to 4% methanol in dichloromethane
customevaporated

Sources & evidence

ORD record: ord-63f7b243b9444ded82b59f57879b9c03
Source dataset: uspto-grants-2000_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06069145

Reaction notes

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