ethyl 1-(5-chloro-2-nitrophenyl)-4-piperidinecarboxylate synthesis

Yield:847408-05-3 100%

Reaction Conditions:

with cesium fluoride in DMF (N,N-dimethyl-formamide) at 0 - 20; for 5 h;

Steps:

36.36A

A solution of 4-CH-LOR-O~2-FLUORONITROBEN- zene (5. 00 g, 28.48 mmol) in dry DMF (30 mL) con- TAINING CsF (4.33 g, 28. 48 mmol) was treated with ethyl isonipecotate (4.82 mL, 31.33 mmol) under N2 atmosphere at 0°C for 1 h and then at ambient tem- perature for 4 h. The reaction mixture was diluted with EtOAc (150 ML) AND washed with water (2X50 mL). The organic layer was separated, dried (MGSO4), fil- tered and evaporated to dryness to provide the title compound (9.31 g, 105% crude yield) as a yellow color LIQUID. 1H NMR (400 MHz, DMSO-d6) 5 7.86 (d, J=8.58 Hz, 1H), 7.32 (d, J=2. 34 Hz, 1H), 7.11 (d, d, J1=2. 34 Hz, J2=8. 58 Hz, 1H), 4.09 (q, J=7.02 Hz, 2H), 3.22-3. 17 (m, 2H), 2.93-2. 87 (M, 2H), 2.54-2. 52 (m, 1H), 1.91-1. 87 (m, 2H), 1.71-1. 61 (m, 2H), 1.19 (t, J=7. 02 Hz, 3H). LCMS (APCI+; Method D) m/z 313, (M+H) +. Analytical HPLC (Method E) Rt=3.656 min (220 nm, 100 AREA%).

References:

WO2005/19200,2005,A2 Location in patent:Page/Page column 184-185