Pyridine → Tert-butyl 4-(chlorocarbonyl)piperazine-1-carboxylate

Temperatur

0 °C

A solution of tert-butyl piperazine-1-carboxylate (210 mg, 1.13 mmol) and pyridine (137 mg, 1.73 mmol) in anhydrous CH2Cl2 (2 mL) was cooled to 0° C. under an atmosphere of N2, treated with a solution of triphosgene (402 mg, 1.35 mmol) in anhydrous CH2Cl2 (2 mL) and stirred at 0° C. for 1 h. The cooling bath was then removed and the reaction stirred at room temperature for a further 1 h. After this time, the mixture was diluted with 1 M hydrochloric acid (25 mL) and extracted with CH2Cl2 (3×20 mL). The combined organic extracts were washed with brine (20 mL), dried over Na2SO4 and the drying agent removed by filtration. The filtrate was concentrated to dryness under reduced pressure to provide tert-butyl 4-(chlorocarbonyl)piperazine-1-carboxylate as a white solid (280 mg, 100%): 1H NMR (500 MHz, CDCl3) δ 10.76 (br s, 1H), 7.33 (dd, J=17.0, 9.0 Hz, 1H), 7.11 (dd, J=9.0, 4.0 Hz, 1H), 4.88-4.52 (m, 2H), 4.69 (br s, 2H), 4.62 (s, 2H), 3.49 (apparent t, J=4.5 Hz, 4H), 3.32 (apparent t, J=4.5 Hz, 4H), 3.25 (apparent t, J=12.5 Hz, 1H), 3.14-2.88 (m, 2H), 1.94 (d, J=12.5 Hz, 2H), 1.72-1.66 (m, 2H), 1.48 (s, 9H).

1. customThe cooling bath was then removed
2. stirringthe reaction stirred at room temperature for a further 1 h
3. additionAfter this time, the mixture was diluted with 1 M hydrochloric acid (25 mL)
4. extractionextracted with CH2Cl2 (3×20 mL)
5. washThe combined organic extracts were washed with brine (20 mL)
6. dry with materialdried over Na2SO4
7. customthe drying agent removed by filtration
8. concentrationThe filtrate was concentrated to dryness under reduced pressure

ORD-Eintrag

ord-1cb835bdcc404c5b9defdf89ab0bfc74

Quelldatensatz

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09434727B2