Chloroacetyl chloride → 2-[4-(2-chloro-acetyl)-piperazin-1-yl]-N-phenyl-benzamide

HRID 1810960Notes

Reaction equation

FC(F)(F)C(O)=O.[C:8]1([NH:14][C:15]([C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=2[N:23]2[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]2)=[O:16])[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1.C(N(C(C)C)CC)(C)C.[Cl:38][CH2:39][C:40](Cl)=[O:41]>C(Cl)Cl>[Cl:38][CH2:39][C:40]([N:26]1[CH2:27][CH2:28][N:23]([C:18]2[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=2[C:15]([NH:14][C:8]2[CH:9]=[CH:10][CH:11]=[CH:12][CH:13]=2)=[O:16])[CH2:24][CH2:25]1)=[O:41]

Participants

Conditions

Temperature: 4 °C

Procedure

4-(2-phenylcarbamoyl-phenyl)-piperazine trifluroacetate (0.454 g, 1.150 mmol) is dissolved in 10 mL of CH2Cl2 containing diisopropylethyl amine (0.554 mL, 3.000 mmol). The mixture is cooled to 4° C. and chloroacetyl chloride (0.105 mL, 0.130 mmol) is added in a dropwise fashion. The reaction is stirred for 2 h in ice bath and then quenched with 20 mL of saturated NH4Cl. The reaction is diluted with 100 mL EtOAc and washed with 2×20 mL of H2O and 1×20 mL of brine. The organic phase is dried with MgSO4, filtered and concentrated. The crude product is purified via a SiO2 column and (0-75% EtOAc/hexanes) to give 310 mg of 2-[4-(2-chloro-acetyl)-piperazin-1-yl]-N-phenyl-benzamide in 75% yield.

Workup

customquenched with 20 mL of saturated NH4Cl
additionThe reaction is diluted with 100 mL EtOAc
washwashed with 2×20 mL of H2O and 1×20 mL of brine
dry with materialThe organic phase is dried with MgSO4
filtrationfiltered
concentrationconcentrated
customThe crude product is purified via a SiO2 column and (0-75% EtOAc/hexanes)

Sources & evidence

ORD record: ord-bc28fe4fe7724eb4939466cdb15824ef
Source dataset: uspto-grants-2013_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08362249B2

Reaction notes

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