(S)-3-N-Boc-aminopiperidine

Chemical Properties

White powder

Uses

(S)-3-(Boc-amino)piperidine, is used as an intermediate for pigments. It is also used as important raw material and intermediate used in organic Synthesis, pharmaceuticals, agrochemicals and dyestuff. It is also an useful intermediate for the synthesis of a variety of chiral aminopiperidinyl quinolones as potent antibacterial agents against resistant pathogens; and alkynylpyrimidine amide derivatives as orally available inhibitors of Tie-2 kinase.

Uses

(S)-3-N-Boc-aminopiperidine can be useful intermediate for the synthesis of a variety of chiral aminopiperidinyl quinolones as potent antibacterial agents against resistant pathogens; and alkynylpyrimidine amide derivatives as orally a vailable inhibitors of Tie-2 kinase.

Synthesis

General procedure for the synthesis of (S)-3-Boc-aminopiperidine from tert-butyl (S)-2-piperidone-3-carbamate: to a solution of THF (250 mL) of the product of Example 41A (20.1 g, 94 mmol) was added slowly and dropwise over a period of 45 min at 0 °C a borane-THF complex (162 mL, 1 M solution of THF 162 mmol; purchased from Aldrich). After the dropwise addition was completed, the reaction was kept at 0 °C with continued stirring for 1 hour. Subsequently, the ice bath was removed and the reaction mixture was allowed to stir at 20-25 °C for 6 hours. Upon completion of the reaction, methanol (100 mL) and 5% NaHCO3 solution (300 mL) were carefully added to quench the reaction. The mixture was stirred vigorously for 16 hours and subsequently concentrated under reduced pressure to reduce the volume. The residue was treated with methanol (200 mL), heated to reflux for 30 minutes, and then concentrated again under reduced pressure. This process was repeated twice. The final residue was suspended in 20% K2CO3 solution (200 mL) and extracted with ether (3 x 200 mL). The organic phases were combined, dried over MgSO4 and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (eluent ratio of dichloromethane: methanol: NH4OH = 90:10:1) to afford (S)-3-Boc-aminopiperidine (5.64 g, 30% yield) in white solid form. The mass spectrum (CI/NH3) showed m/z 201 (M + H)+.

References

[1] Patent: EP1428824, 2004, A1. Location in patent: Page 44