Bromine → 4-(Bromo-cyano-methylidene)-piperidine-1-carboxylic acid tert-butyl ester

A slurry of sodium hydride (0.76 g, 19.0 mmol) in THF (75 mL) at 0° C. under nitrogen was carefully treated with diethyl cyanomethylphosphonate (3.4 g, 19.0 mmol) via a syringe. After gas evolution ceased, the reaction mixture was treated with bromine (3.04 g, 19.0 mmol) via a dropping funnel over 10 min., and the resulting mixture was allowed to stir for 2 h. The reaction mixture was treated with sodium hydride (0.76 g, 19.0 mmol) and the resulting slurry was allowed to stir for 30 min. at 0° C. A solution of 1-(tert-butoxycarbonyl)-4-piperidinone (2.52 g, 12.7 mmol) in THF (10 mL) was added dropwise over 10 min. and the resulting solution was allowed to stir at room temperature overnight. The reaction was quenched by the addition of water (50 mL) and the resulting mixture was diluted with ethyl acetate (100 mL), washed with sat. NH4Cl (100 mL), brine (100 mL), and concentrated in vacuo. Purification by chromatography (EtOAc/hexanes=1:4) yielded the title compound (2.8 g, 74%) as a white solid. MS 301 (M+H).

1. stirringto stir for 30 min. at 0° C
2. stirringto stir at room temperature overnight
3. customThe reaction was quenched by the addition of water (50 mL)
4. additionthe resulting mixture was diluted with ethyl acetate (100 mL)
5. washwashed with sat. NH4Cl (100 mL), brine (100 mL)
6. concentrationconcentrated in vacuo
7. customPurification by chromatography (EtOAc/hexanes=1:4)

ORD-Eintrag

ord-a1bcd9af93f44d31a482984567698e35

Quelldatensatz

uspto-grants-2010_06

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07732612B2