METHYL N-4-BOC-N-1-CBZ-2-PIPERAZINECARBOXYLATE Chemical Properties

Boiling point:

476.9±45.0 °C(Predicted)

Density 

1.214±0.06 g/cm3(Predicted)

storage temp. 

Sealed in dry,Room Temperature

pka

-1.49±0.70(Predicted)

Appearance

White to off-white Solid

METHYL N-4-BOC-N-1-CBZ-2-PIPERAZINECARBOXYLATE Usage And Synthesis

Application

METHYL N-4-BOC-N-1-CBZ-2-PIPERAZINECARBOXYLATE, also known as 1-benzyl4-(tert-butyl)2-methylpiperazine-1,2,4-tricarboxylate, is a pharmaceutical intermediate that can be obtained by esterification with piperazine-2-carboxylic acid as a starting material, followed by Boc protection, Cbz protection, and finally iodomethane.

Synthesis

The fully protected Methyl N-4-Boc-N-1-Cbz-2-piperazinecarboxylate was prepared from 2-piperazinecarboxylic acid as shown in the below  figure. Using a sequential one-pot protection procedure similar to that used to protect lysine, a solution of 2-piperazinecarboxylic acid (24.1 g, 0.185 mol) in 1:1 dioxane-water (1.2 L) was maintained at pH 11 with 50% aqueous sodium hydroxide during the addition of a solution of 2-(t-butyloxycarbonyloxyimino)-2-phenylacetonitrile (BOC-ON, 51 g, 0.21 mol) in dioxane (0.3 L). After 3 h, the reaction mixture was cooled in an ice bath and the pH was adjusted to pH 9.5 with 6 N HCl. Benzylchloroformate was added dropwise to the cold solution while maintaining the pH with 50% aqueous sodium hydroxide. The reaction was warmed to room temperature and stirred for 24 h. The solution was washed with diethyl ether (4 x 250 mL), the aqueous layer was acidified to pH 2 and extracted with ethyl acetate (4 x 250 mL) . The organic layer was dried over magnesium sulfate, filtered and evaporated to give a pale yellow oil.
The methyl ester 5(Methyl N-4-Boc-N-1-Cbz-2-piperazinecarboxylate) was obtained by treatment of a tetrahydrofuran solution of the crude acid with excess diazomethane. Alternatively, the methyl ester could be obtained on large scale by treatment of a saturated sodium bicarbonate solution of the intermediate carboxylic acid 4 with a methylene chloride solution of methyl iodide and Adogen 464, or preferably by refluxing an acetone solution of the carboxylic acid, dimethyisulfate and potassium carbonate.^[1]

References

[1] CHRISTOPHER F BIGGE ∗. New preparations of the N-methyl-D-aspartate receptor antagonist, 4-(3-phosphonopropyl)-2-piperazinecarboxylic acid (CPP)[J]. Tetrahedron Letters, 1989, 30 39: Pages 5193-5196. DOI:10.1016/S0040-4039(01)93739-6.

METHYL N-4-BOC-N-1-CBZ-2-PIPERAZINECARBOXYLATE(126937-42-6)Related Product Information

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