ChemicalBook CAS DataBase List 4-BENZYLIDENE-PIPERIDINE-1-CARBOXYLIC ACID TERT-BUTYL ESTER

4-BENZYLIDENE-PIPERIDINE-1-CARBOXYLIC ACID TERT-BUTYL ESTER synthesis

14synthesis methods

Product Name:4-BENZYLIDENE-PIPERIDINE-1-CARBOXYLIC ACID TERT-BUTYL ESTER
CAS Number:193217-39-9
Molecular formula:C17H23NO3
Molecular Weight:289.37

37586-22-4 Synthesis

37586-22-4
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$541.82/5g

24424-99-5 Synthesis

24424-99-5
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$13.50/25G

4-BENZYLIDENE-PIPERIDINE-1-CARBOXYLIC ACID TERT-BUTYL ESTER

193217-39-9
68 suppliers
$75.00/100mg

Yield: 90%

Reaction Conditions:

Stage #1:4-benzoylpiperidine with sodium hydrogencarbonate in water at 20; for 0.25 h;
Stage #2:di-tert-butyl dicarbonate in water at 20; for 15 h;

Steps:

6
To a mixture of NaHC0₃ (173 g) and water (1.5 L) was added compound 11a of J. Med. Chem. 2003, vol 46, 25, 5512-5532 (119.3 g, 0.63 mol). The reaction was stirred at room temperature for 15 min and then (Boc)₂0 was added. After stirring for 15 h at room temperature a white solid was filtered and washed with water to affor 164 g (Yield: 90 %, mp 91-93 °C) of 4-benzoyl-l-[(l,l-dimethylethyloxy)carbonyl]piperidine. A suspension of Mg turnings (1.0 g) in anhydrous diethyl ether (40 mL) was prepared and treated with 1/3 of a solution of 4-chlorobenzyl chloride (4.6 g, 27.0 mmol) in anhydrous diethyl ether (40 mL) and an iodine crystal. The mixture was heated until a smooth reflux was observed and the color disappeared. The rest of the solution of 4- chlorobenzyl chloride was added. The reflux was continued for 3.5 h and the reaction mixture cooled to room temperature. A solution of 4-benzoyl-l-[(l,l- dimethylethyloxy)carbonyl]piperidine (6.4 g, 22.4 mmol) in anhydrous diethyl ether (50 mL) was added dropwise and the reaction refluxed for 3h. A saturated aqueous NH₄C1 solution (50 mL) was added, the diethyl ether evaporated and the mixture extracted with CHC1₃. The organic layer was dried over anhydrous Na₂S0₄, filtered and concentrated in vacuo to give to give a solid which was washed with hexane. This solid was dissolved in chloroform (100 mL), treated with trifluoro acetic acid (8 mL) and refluxed for 15 h. The reaction mixture was cooled to room temperature, treated with 10 % aqueous NaOH solution and extracted with chloroform. The organic layer was dried over anhydrous Na₂S0₄, filtered and evaporated under reduced pressure to afford a mixture E/Z isomers. Purification by flash chromatography on silica gel (Diethyl etherTsopropilamine 10/0.5) gave 1.6 g of the Z isomer of the title compound (Yield: 22 %, mp 121-124 °C).

References:

FAES FARMA, S.A.;LEDO GÓMEZ, Francisco;MUÑOZ MUÑOZ, Ana;PUMAR DURÁN, Carmen WO2011/147780, 2011, A1 Location in patent:Page/Page column 30

24424-99-5 Synthesis

24424-99-5
821 suppliers
$13.50/25G

25519-80-6 Synthesis