N,N-Dimethylaniline → 5-Benzyloxycarbonylamino-2-(4-methyl-3-oxopiperazin-1-yl)fluorobenzene

HRID 1108570Notes

Reaction equation

[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([N:9]2[CH2:14][CH2:13][N:12]([CH3:15])[C:11](=[O:16])[CH2:10]2)=[C:6]([F:8])[CH:7]=1.CN(C)C1C=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]>CN(C=O)C.C(OCC)(=O)C>[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]([CH3:15])[C:11](=[O:16])[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-methyl-3-oxopiperazin-1-yl)fluorobenzene (2.94 g) was dissolved in dry DMF (40 ml) under argon, and the solution cooled to -20° C. N,N-Dimethylaniline (2.1 ml) was added, followed by benzyl chloroformate (2.07 ml), and the mixture stirred for 10 minutes at -20° C. The temperature was allowed to rise to ambient over 16 hours. The mixture was diluted with ethyl acetate, and washed twice with water, and then brine. After drying (MgSO4) and evaporation of solvent, the residue was chromatographed on silica, using as eluant a gradient increasing in polarity from 0 to 5% methanol in dichloromethane. Relevant fractions were combined and evaporated to give 5-benzyloxycarbonylamino-2-(4-methyl-3-oxopiperazin-1-yl)fluorobenzene (4.6 g).

Workup

waitto ambient over 16 hours
washwashed twice with water
customAfter drying
custom(MgSO4) and evaporation of solvent
customthe residue was chromatographed on silica
temperaturea gradient increasing in polarity from 0 to 5% methanol in dichloromethane
customevaporated

Sources & evidence

ORD record: ord-d748b4cf864242f8a1950bc12750be38
Source dataset: uspto-grants-2000_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US06069145

Reaction notes

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