Yield:848488-91-5 100%

Reaction Conditions:

with ammonium chloride;N-ethyl-N,N-diisopropylamine;HATU in DMF (N,N-dimethyl-formamide) at 0 - 20; for 18 h;

Steps:

77.B

Step B. tert-Butyl (2R)-2-(aminocarbonyl)piperidine-1-carboxylate; HATU (5.60 g, 14.7 mmol) was added to a mixture of the (2R)- 1 -(tert- butoxycarbonyl) piperidine-2-carboxylic acid (2.29 g, 10 mmol), ammonium chloride (3.21 g, 60 mmol) and DIPEA (3.88 g, 30 mmol) in DMF (70 mL) at 0 °C. The mixture was stirred for 18 h at room temperature, diluted with H20 (100 mL) and extracted with EtOAc (3x100 mL). The combined organic phases were washed with 10% Na2C03 solution (2x30 mL), brine (2x30 mL) and dried with Na2S04. After filtration and concentration, the title compound was purified by MPLC on silica gel using hexane/EtOAc (1:1) g, 100 %) as a white solid. (at)H NMR(400 MHz, CDCl3) No. 1.46 (s, 9 H), 1.63 (m, 2 H), 2.22 (m, 1 H), 2.91 (m, 1 H), 3.06 (m, 3 H), 4.01 (m, 1 H), 4.71 (m, 1 H), 6.46 (s broad, 2 H). MS (ESI) (M+H) (at)= 228.92

References:

WO2005/115986,2005,A1 Location in patent:Page/Page column 103