Chloroacetyl chloride → N-(2-methoxy-1-methylethyl)-2-piperazin-1-yl-acetamide dihydrochloride

Temperatur

-40 °C

Methoxy-1-methyl-ethylamine (15 mmol, 1.15 eq) and diisopropylethylamine (17 mmol, 1.3 eq) were diluted with methylene chloride to give a total volume of 8 mL. The amine solution was added in a portion-wise fashion via a syringe to a solution of chloroacetylchloride (13 mmol) in methylene chloride (10 mL) cooled to approximately −40° C. in a sealed 40 mL vial. The reaction mixture was stirred for 1 h at reduced temperature. The solution was then made acidic with 1N HCl and then diluted with 10 mL of methylene chloride. The vial was agitated and centrifuged. The organic layer was transferred to 40 ml, vials and concentrated in vacuo. The residue (1.69 g, 10.21 mmol) was diluted with 10 mL of dimethylformamide. Piperazine-1-carboxylic acid tert-butyl ester (8.67 mmol, 0.85 eq) and diisopropylethylamine (13.27 mmol, 1.3 eq) were added. The reaction mixture was shaken at 65° C. overnight and concentrated in vacuo. The crude residue was dissolved in 10 mL of dioxane and 10 mL of 4M hydrochloric acid in dioxane. The solution was shaken overnight at room temperature then centrifuged. The supernatant was removed, and the remaining solids were shaken with hexane then centrifuged. The supernatant was removed, and the solids was collected and dried in vacuo to give N-(2-methoxy-1-methylethyl)-2-piperazin-1-yl-acetamide dihydrochloride. LR-MS: 216.4 [(M+H)+]

1. customto give a total volume of 8 mL
2. stirringThe vial was agitated
3. concentrationconcentrated in vacuo
4. stirringThe reaction mixture was shaken at 65° C. overnight
5. concentrationconcentrated in vacuo
6. dissolutionThe crude residue was dissolved in 10 mL of dioxane
7. stirringThe solution was shaken overnight at room temperature
8. customThe supernatant was removed
9. stirringthe remaining solids were shaken with hexane
10. customThe supernatant was removed
11. customthe solids was collected
12. customdried in vacuo

ORD-Eintrag

ord-f55f942df4b14ed18ac9b67ee817a3f7

Quelldatensatz

uspto-grants-2011_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07964724B2