1-BOC-4-FLUORO-4-PIPERIDINECARBOXYLIC ACID synthesis

Yield:-

Reaction Conditions:

Stage #1:4-fluoro-1-(1,1-dimethylethyl)-1,4-piperidinedicarboxylic acid 4-methyl ester with sodium hydroxide;ethanol;water at 20 - 60;
Stage #2: with hydrogenchloride;water in ethanol

Steps:

1
Description 1 (DD 1-fr(1.1-Dimethylethyl)oxy1carbonyl)-4-fluoro-4-piperidinecarboxylic acid Solution of 4-fluoro-1-(1 ,1-dimethylethyl)-1 ,4-piperidine dicarboxylic acid -4-methyl ester (1.00 g, 4.02 mmol) in EtOH (16 ml) was stirred at room temperature. 2M NaOH (5.0 ml, 10.05 mmol) was added and the solution heated to 60 ⁰C for 5 % hours. After this time, the solution was left to cool to room temperature overnight. The solution was then acidified using 2M HCI and the organics were extracted into EtOAc (x 2). The combined organics were dried over MgSO₄, filtered and concentrated under reduced pressure to give a white coloured solid (0.767 g)

References:

GLAXO GROUP LIMITED WO2008/98978, 2008, A2 Location in patent:Page/Page column 32-33