Diphosgene → 4-Cbz-piperazine-1-carbonyl Chloride
Reaction equation
[Cl:1][C:2](OC(Cl)(Cl)Cl)=[O:3].[N:9]1([C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:16])[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]1.C(N(CC)C(C)C)(C)C>O1CCCC1>[Cl:1][C:2]([N:12]1[CH2:13][CH2:14][N:9]([C:15]([O:17][CH2:18][C:19]2[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=2)=[O:16])[CH2:10][CH2:11]1)=[O:3]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 1
Conditions
- Temperature
- 0 °C
Procedure
Trichloromethyl chloroformate (5.45 mmol, 0.657 ml) in tetrahydrofuran (20 ml) was cooled to 0° C. and a solution of benzyl 1-piperazinecarboxylate (4.54 mmol, 0.876 ml) and N,N-diisopropylethylamine (9.99 mmol, 1.651 ml) in tetrahydrofuran (20 ml) was added dropwise. After stirring for one hour at 0° C. the solids were removed by filtration over decalite and the filtrate was concentrated in vacuo to give crude benzyl 4-(chlorocarbonyl)piperazine-1-carboxylate. The latter compound was added to 2-aminomethyl-3-chloropyrazine hydrochloride (content 69%; 3.49 mmol, 0.91 g) in dichloromethane (15 ml) and triethylamine (10.46 mmol, 1.458 ml) and the reaction mixture was stirred over night at room temperature. Then the reaction mixture was filtered over decalite (washed with dichloromethane). The filtrate was concentrated and the crude product was purified using column chromatography (silica gel; dichloromethane with gradient 0 to 10% methanol) to give benzyl 4-((3-chloropyrazin-2-yl)methylcarbamoyl)piperazine-1-carboxylate (1.15 g).
Workup
- customwere removed by filtration over decalite
- concentrationthe filtrate was concentrated in vacuo
Sources & evidence
- ORD record
- ord-93d41685d4594b559bf4b545dc029326
- Source dataset
- uspto-grants-2014_02
- Patent number
- US08658794B2
Reaction notes
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