1-BOC-4-CYANO-4-(3-METHOXYPHENYL)-PIPERIDINE synthesis

Yield:553631-35-9 88.3 %

Reaction Conditions:

with sodium hydride in N,N-dimethyl-formamide;mineral oil at 70;

Steps:

50.1 Step 1

Tert-butyl 4-cyano-4-(3-methoxyphenyl)piperidine-1-carboxylate 2-(3-methoxyphenyl)acetonitrile 50a (2 g,13.59 mmol) and tert-butyl bis(2-chloroethyl)carbamate (3.62 g, 14.95 mmol) were dissolved in N,N-dimethylformamide(12 mL), added with 60% sodium hydride (2.17 g, 54.36 mmol) in batches, stirred for 40 minutes, heated to 70°C, andreacted overnight. The reaction solution was cooled to room temperature, quenched with water (100 mL), and extractedwith ethyl acetate (100 mL33). Organic phases were combined, washed with a saturated sodium chloride solution (100mL), dried with anhydrous sodium sulfate and concentrated under reduced pressure. The obtained residue was purifiedby silica gel column chromatography (eluent: system A) to obtain tert-butyl 4-cyano-4-(3-methoxyphenyl)piperidine-1-carboxylate 50b (3.8 g) with a yield of 88.3%.MS m/z (ESI): 217.0 [M-99]

References:

EP4092019,2022,A1 Location in patent:Paragraph 0280-0281