Ethyl 4-piperidinecarboxylate → Ethyl 1-carbamothioylpiperidine-4-carboxylate

To a solution (200 mL) of 1,1′-thiocarbonyldiimidazole (15.0 g) in tetrahydrofuran was added ethyl piperidine-4-carboxylate (12.59 g) at room temperature, and the mixture was stirred at room temperature for 3 hrs and then at 55° C. for 1 hr. Tetrahydrofuran (ca. 100 mL) was distilled off under reduced pressure and 2M ammonia methanol solution (150 mL) was added. After stirring the reaction mixture at room temperature for 15 hrs, the mixture was concentrated. The residue was diluted with ethyl acetate and washed successively with water and saturated brine. The organic layer was dried over anhydrous magnesium sulfate and concentrated. The residue was subjected to silica gel column chromatography and eluted with ethyl acetate-hexane (2:1, v/v) to give ethyl 1-(aminocarbonothioyl)piperidine-4-carboxylate as colorless crystals (4.76 g, yield 27%). The crystals were recrystallized from ethyl acetate-hexane. melting point: 97-98° C.

1. waitat 55° C. for 1 hr
2. distillationTetrahydrofuran (ca. 100 mL) was distilled off under reduced pressure and 2M ammonia methanol solution (150 mL)
3. additionwas added
4. stirringAfter stirring the reaction mixture at room temperature for 15 hrs
5. concentrationthe mixture was concentrated
6. additionThe residue was diluted with ethyl acetate
7. washwashed successively with water and saturated brine
8. dry with materialThe organic layer was dried over anhydrous magnesium sulfate
9. concentrationconcentrated
10. washeluted with ethyl acetate-hexane (2:1

ORD record

ord-1f2e9ad855764001ae7b0a48d19ce567

Source dataset

uspto-grants-2008_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07368578B2