Sodium Carbonate → 1-Benzyl-5-(4-chloro-phenyl)-1,2,3,6-tetrahydro-pyridine-4-carboxylic acid ethyl ester

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Reaction Conditions

Reaction Steps

In a 1500 mL four necked flask (with mechanical stirrer) 22 g (84.2 mmol) ethyl N-benzyl-3-oxo-4-piperidine-carboxylate (from the HCl-salt by aq.Na2CO3/CH2Cl2-extraction) and 43.5 mL (252 mmol) DIPEA were dissolved in 300 mL DCM. The amber solution was cooled to −20° C. to −30° C. 28.5 g (101 mmol) trifluoromethanesulfonic anhydride were added drop wise over a period of 45 min. The dark brown solution was stirred for 2 h at −20° C./−30° C. 300 mL water and 300 mL 10% Na2CO3 aq. was added and the mixture was stirred for 15 min at 5-10° C. The organic layer was separated and the aqueous layer was extracted twice with 150 mL DCM. The combined organic layers were dried over Na2SO4 and filtered. The filtrate was evaporated to dryness and dissolved in 500 mL dioxane. 15.8 g (101 mmol) 4-chlorophenylboronic acid, 93 mL Na2CO3 aq. (2M) and 3.8 g (3.36 mmol) tetrakis(triphenylphosphine)palladium(0) was added and the mixture was heated to reflux over night. After cooling to room temperature, the mixture was diluted with 400 g ice-water and extracted twice with 400 mL ethyl acetate. The organic layers were extracted once with 500 mL brine. After drying over Na2SO4 the filtrate was evaporated to dryness. The black oil was absorbed on 60 g isolute HM-N and purified by column chromatography to yield 14.6 g (48%) of the title compound as viscous yellow oil. MS (m/e): 356.3 [(M+H)+].

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