ChemicalBook CAS DataBase List 1-BENZYL 4-ETHYL PIPERIDINE-1,4-DICARBOXYLATE

1-BENZYL 4-ETHYL PIPERIDINE-1,4-DICARBOXYLATE synthesis

3synthesis methods

Product Name:1-BENZYL 4-ETHYL PIPERIDINE-1,4-DICARBOXYLATE
CAS Number:160809-38-1
Molecular formula:C16H21NO4
Molecular Weight:291.34

1126-09-6

501-53-1

1-BENZYL 4-ETHYL PIPERIDINE-1,4-DICARBOXYLATE

160809-38-1

The general procedure for the synthesis of ethyl 1-Cbz-piperidine-4-carboxylate from ethyl 4-piperidinecarboxylate and benzyl chloroformate was as follows: a solution of benzyl chloroformate (95 g, 0.56 mol) in dichloromethane (200 mL) was added slowly and dropwise to a stirred ethyl 4-piperidinecarboxylate (87 g, 0.55 mol) and sodium carbonate (60 g, 0.57 mol) mixture. The dropwise addition was controlled to be completed in 70 min, during which dichloromethane (200 mL) was added simultaneously. The reaction mixture was stirred continuously at room temperature for 2.5 days, followed by filtration through a Celte pad. The filtrate was concentrated under vacuum and the residue was partitioned between 2M aqueous hydrochloric acid and ether. The organic layer was separated, dried with anhydrous magnesium sulfate, filtered and concentrated. Finally, the residue was purified by silica gel column chromatography (eluent: ethyl acetate/isohexane) to afford the target product ethyl 1-Cbz-piperidine-4-carboxylate (152 g, 94% yield). The product was characterized by 1H NMR (360 MHz, CDCl3): δ 7.40-7.27 (5H, m), 5.12 (2H, s), 4.22-3.99 (2H, m), 4.40 (2H, q, J=7.4 Hz), 2.93 (2H, br t, J=11.6 Hz), 2.45 (2H, m), 1.97-1.81 (2H, m), 1.74-1.56 (2H, m), 1.25 (3H, t, J=7.4 Hz).

1126-09-6 Synthesis

1126-09-6
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501-53-1
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160809-38-1
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$38.00/1g

Yield: 94%

Reaction Conditions:

with sodium carbonate in dichloromethane at 0 - 20; for 60 h;

Steps:

1 DESCRIPTION 1; Piperidine-1, 4-dicarboxylic acid 1-benzyl ester 4-ethyl ester
A solution of benzyl chloroformate (95g, 0. 56mol) in dichloromethane (200ml) was added dropwise to an ice-bath-cooled, stirred mixture of ethyl isonipecotate (87G, 0. 55MOL), sodium carbonate (60g, 0. 57mol) and dichloromethane (200ml) over 70 minutes. The mixture was stirred at ambient temperature for 2.5 days and filtered though a pad of Celte. The filtrate was concentrated in vacuo. The residue was partitioned between 2M aqueous hydrochloric acid and diethyl ether. Organic layer was separated, dried (MGS04), filtered and concentrated. The residue was chromatographed on silica gel (ethyl ACETATE/ISO-HEXANE) to give the title product (152g, 94%). lE NMR (360 MHz, CDCl3) : 5 7. 4 1-7. 27 (5H, M), 5.12 (2EI, s), 4.22-3. 99 (2H, M), 4. 14 (2H, Q, J7. 4HZ), 2.93 (2H, br T, J 11. 6HZ), 2.45 (2H, m), 1.97-1. 81 (2H, M), 1.74-1. 56 (2EI, m), 1. 25 (3H, T, J7. 4Hz).

References:

MERCK SHARP & DOHME LIMITED WO2004/78750, 2004, A1 Location in patent:Page 64