Hydrogen Peroxide → HCID 58117117, compound

To a mixture of tetrahydro-4H-pyran-4-one (500 mg, 5.00 mmol) and 1-Boc-piperazine (930 mg, 5.00 mmol) in methanol (10 mL) at 0° C. was added dropwise a solution of potassium cyanide (325 mg, 5.00 mmol) in water (1 mL). The mixture was warmed to room temperature and stirred overnight. The mixture was partitioned between ethyl acetate and water. The combined organic layers were washed with brine, separated and dried (MgSO4) to yield a 1:1 mixture of 4-(4-cyano-tetrahydro-pyran-4-yl)-piperazine-1-carboxylic acid tert-butyl ester and unreacted starting material (1.15 g). The crude mixture was dissolved in methanol (10 mL) and 1M sodium hydroxide solution (5 mL, 5.00 mmol) was added followed by the dropwise addition of hydrogen peroxide, (30 wt % solution in water; 2.5 mL) The mixture was stirred at room temperature overnight. The mixture was evaporated in vacuo and the crude product was purified by column chromatography to yield 4-(4-carbamoyl-tetrahydro-pyran-4-yl)-piperazine-1-carboxylic acid tert-butyl ester (307 mg). Removal of the Boc-protecting group using 2.0 M HCl in diethyl ether in dichloromethane gave the di-hydrochloride salt of the title compound as a pale solid (260 mg).

1. customThe mixture was partitioned between ethyl acetate and water
2. washThe combined organic layers were washed with brine
3. customseparated
4. dry with materialdried (MgSO4)
5. customto yield
6. stirringwas stirred at room temperature overnight
7. customThe mixture was evaporated in vacuo
8. customthe crude product was purified by column chromatography

ORD record

ord-667581e1ed8e4832af314f88e04099d5

Source dataset

uspto-grants-2012_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08293735B2