ETHYL N-BOC-4-(4-FLUOROBENZYL)PIPERIDINE-4-CARBOXYLATE synthesis

Yield:917755-77-2 89.2%

Reaction Conditions:

Stage #1: 1-tert-butyl 4-ethyl piperidine-1,4-dicarboxylatewith lithium diisopropyl amide in tetrahydrofuran at -78 - -40; for 1 h;
Stage #2: 4-Fluorobenzyl bromide in tetrahydrofuran at -78; for 2 h;Product distribution / selectivity;

Steps:

82.1

Step-1: 4-(4-Fluoro-benzyl)-piperidine-1,4-dicarboxylic acid 1-tent-butyl ester 4-ethyl ester; To a stirred solution of lithium diisopropyl amide in THF was added Piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester (2 g, 7.7 mmol) at -78° C. The reaction mixture was stirred at -40° C. for 1 hr. Then reaction mixture was cooled to -78° C. and was added 4-fluorobenzyl bromide (1.46 g, 7.7 mmole) was added to reaction mass at -78° C. The resulting mixture was stirred at -78° C. for 2 hrs. Then reaction mixture was quenched with saturated ammonium chloride solution and extracted with ethyl acetate. Organic layer was washed with water and brine, dried over Na₂SO₄ and concentrated under reduced pressure. The crude mass was washed with hexane to afford 2.5 g (89.2%) of 4-(4-Fluoro-benzyl)-piperidine-1,4-dicarboxylic acid 1-tert-butyl ester 4-ethyl ester. LC/MS [M+H]⁺: 366.3.

References:

US2010/152160,2010,A1 Location in patent:Page/Page column 77