Isopropyl chloroformate → 4-Hydrazino-piperidine-1-carboxylic acid isopropyl ester hydrochloride

Triethylamine (8.35 g, 60 mmol) was added to a mixture of 4-oxopiperidine hydrate hydrochloride (4.61 g, 30 mmol) and tetrahydrofuran (200 mL) and the resulting poorly soluble mixture was stirred for 1 h. Isopropyl chloroformate (3.3 mL, 34.7 mmol) was added and the mixture was stirred overnight and then filtered. The solvent was evaporated to give a crude intermediate which was dissolved in methanol (80 mL). tert-Butyl carbazate (26 mmol) was added and the mixture was stirred for 2 h. Volatiles were evaporated to give an oil which was dissolved in 50% aqueous acetic acid (80 mL). Sodium cyanoborohydride (35 mmol) was added and the mixture was stirred for 3 h. The reaction mixture was neutralized with 3 M aqueous sodium hydroxide and then extracted three times with dichloromethane. The combined organic extracts were dried, filtered, and evaporated. HCl in dioxane (4 M; 25 mL) and methanol (20 mL) were added and the mixture was stirred for 1 h. Volatiles were evaporated to give 4-hydrazino-piperidine-1-carboxylic acid isopropyl ester hydrochloride (4.02 g, 56%) as a white solid.

1. stirringthe mixture was stirred overnight
2. filtrationfiltered
3. customThe solvent was evaporated
4. customto give a crude intermediate which
5. stirringthe mixture was stirred for 2 h
6. customVolatiles were evaporated
7. customto give an oil which
8. stirringthe mixture was stirred for 3 h
9. extractionextracted three times with dichloromethane
10. customThe combined organic extracts were dried
11. filtrationfiltered
12. customevaporated
13. additionHCl in dioxane (4 M; 25 mL) and methanol (20 mL) were added
14. stirringthe mixture was stirred for 1 h
15. customVolatiles were evaporated

ORD record

ord-9d3567916a944be99fa8509b3e939a0f

Source dataset

uspto-grants-2012_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08188098B2