Butyl iodide → 4-Piperidinecarboxylic acid

Temperature

-78 °C

To a solution of 0.88 g (8.6 mmol) of diisopropylethylamine in 30 ml of THF at 0° C. under N2 was added dropwise 3.52 ml (8.6 mmol) of a solution of 2.5N butyl lithium in hexanes. The solution was stirred for 15 minutes, cooled to -78° C. and treated with a solution of ethyl N-BOC-4-piperidinecarboxylate (2.0 g, 8.0 mmol) in 8 ml of THF. The solution was stirred for 1 hour and then 2.16 g (8.4 mmol) of n-butyl iodide was added and the reaction mixture was allowed to warm to room temperature and was stirred over night. The solution was diluted with 100 ml of EtOAc and washed with 1N HCl (3×20 ml); saturated sodium bicarbonate solution (2×20 mL) and brine (1×20 ml). The organic phase was dried over MgSO4, filtered and concentrated in vacuo. The residue was purified by flash chromatography over silica gel eluting with 10% EtOAc/hexanes to give the desired product. 1H-NMR (CDCl3, 400 MHz): 0.86 (t, 3H); 1.25 (t, 3H); 1.93 (s, 9H); 1.1-1.8 (m, 8H); 2.08 (bd, 2H); 2.85 9bt, 2H); 3.85 (bd, 2H); 4.16 (q, 2H).

1. stirringThe solution was stirred for 1 hour
2. temperatureto warm to room temperature
3. stirringwas stirred over night
4. washwashed with 1N HCl (3×20 ml)
5. dry with materialThe organic phase was dried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated in vacuo
8. customThe residue was purified by flash chromatography over silica gel eluting with 10% EtOAc/hexanes

ORD record

ord-10c5a068b2814ddf83da41208e076998

Source dataset

uspto-grants-2000_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06020347