ChemicalBook CAS DataBase List TERT-BUTYL 4-(4-CHLOROPHENYL)-4-CYANOPIPERIDINE-1-CARBOXYLATE

TERT-BUTYL 4-(4-CHLOROPHENYL)-4-CYANOPIPERIDINE-1-CARBOXYLATE synthesis

4synthesis methods

Product Name:TERT-BUTYL 4-(4-CHLOROPHENYL)-4-CYANOPIPERIDINE-1-CARBOXYLATE
CAS Number:218451-34-4
Molecular formula:C17H21ClN2O2
Molecular Weight:320.81

118753-70-1

140-53-4

TERT-BUTYL 4-(4-CHLOROPHENYL)-4-CYANOPIPERIDINE-1-CARBOXYLATE

218451-34-4

Step 1. 2-(4-Chlorophenyl)acetonitrile (20.1 g, 132.59 mmol, 1.00 eq.) and tert-butyl N,N-bis(2-chloroethyl)carbamate (35.4 g, 146.19 mmol, 1.10 eq.) were dissolved in anhydrous DMF (200 mL) protected by nitrogen and cooled to 0°C. The mixture was then dissolved in a mixture of sodium hydroxide (27 g, 60% mineral oil dispersion, 666.73 mmol, 3.00 eq.) and sodium hydride (27 g). Sodium hydride (27 g, 60% mineral oil dispersion, 666.73 mmol, 3.00 eq.) was added in batches over 2 hours. The reaction mixture was stirred at 60 °C for 1.5 h, followed by stirring at room temperature overnight. Upon completion of the reaction, the reaction was quenched by careful addition of 250 mL of saturated aqueous NaHCO3. The reaction mixture was extracted with dichloromethane (3 x 200 mL), the organic phases were combined, washed with brine (2 x 300 mL), dried over anhydrous sodium sulfate and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography with the eluent dichloromethane/petroleum ether (1:1) to afford tert-butyl 4-(4-chlorophenyl)-4-cyanopiperidine-1-carboxylate (30 g, 71%) as a yellow solid.TLC: Rf = 0.15 (Expanding agent: ethyl acetate/petroleum ether=1/5).

118753-70-1 Synthesis

118753-70-1
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140-53-4
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218451-34-4
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Yield:218451-34-4 71%

Reaction Conditions:

with sodium hydride in N,N-dimethyl-formamide;mineral oil at 0 - 60;Inert atmosphere;

Steps:

1d.1

Step 1. To the solution of 2-(4-chlorophenyl)acetonitrile (20.1 g, 132.59 mmol, 1.00 equiv) and tert-butyl N,N-bis(2-chloroethyl)carbamate (35.4 g, 146.19 mmol, 1.10 equiv) in anhydrous DMF (200 mL) was added sodium hydride (27g, 60% in mineral oil,666.73 mmol, 3.00 equiv) portionwise at 0°C under N2 over 2 hr. The resulting solution was stirred at 60°C for 1.5 hr, and then stirred overnight at room temperature. The reaction was quenched by the careful addition of 250 mL of sat. aq. NH4C1. The resulting solution was extracted with 3x200 mL of dichloromethane. The combined extracts were washed with 2x300 mL of brine, then dried over anhydrous sodium sulfate andconcentrated under vacuum. The residue was purified on a silica gel column with dichloromethane/petroleum ether (1:1). 30 g (71%) of tert-butyl 4-(4-chlorophenyl)-4- cyanopiperidine-1-carboxylate was obtained as a yellow solid. TLC: Rf = 0.15; ethyl acetate/petroleum ether = 1/5.

References:

WO2015/32286,2015,A1 Location in patent:Page/Page column 310; 311

623-03-0 Synthesis