ChemicalBook CAS DataBase List 1-Benzyl-4-piperidone

1-Benzyl-4-piperidone synthesis

13synthesis methods

Product Name:1-Benzyl-4-piperidone
CAS Number:3612-20-2
Molecular formula:C12H15NO
Molecular Weight:189.25

1-Benzyl-4-piperidone was synthesized with benzylamine and methyl acrylate as raw materials via 1,4-addition, Dieckmann condensation and hydrolysis decarboxylafion reactions. Add 150 mL of anhydrous toluene and 2.8 g of metallic sodium to a 250 mL dry three-necked flask, stir and heat to reflux. Add 1 mL of anhydrous methanol, then slowly drop 28 g of N.N-bis(β-propionate methyl ester) benzylamine. After adding N.N-bis(β-propionate methyl ester), benzylamine is completed, reflux for 6 h. During the reflux process, the stirring speed needs to be increased, and 100 ml of anhydrous toluene is added to the reaction vessel in batches. Stop reflux, cool to room temperature, extract the mixture with 150 mL of 25% (mass fraction) hydrochloric acid solution, and reflux in an oil bath for 5 h until there is no colour change in the FeCl3 solution test, indicating that the reaction is over. Cool the reaction mixture, add 35% NaOH solution while stirring to neutralize to about pH=8.5, extract with ethyl acetate (100 ml×3), combine the ethyl acetate layers, wash with saturated NaCl solution, and dry over anhydrous magnesium sulfate. Ethyl acetate was recovered by distillation, and the remaining material was distilled under reduced pressure to obtain 14.8 g of 1-benzyl-4-piperidone with a yield of 78.4%. The product was a light yellow oily liquid.

41979-39-9 Synthesis

41979-39-9
117 suppliers
$15.00/10mg

100-39-0
434 suppliers
$10.00/10g

3612-20-2
490 suppliers
$6.00/10g

Yield:3612-20-2 89.28%

Reaction Conditions:

Stage #1: 4-piperidone hydrochloridewith potassium carbonate in N,N-dimethyl-formamide at 20; for 0.5 h;
Stage #2: benzyl bromide in N,N-dimethyl-formamide at 65; for 14 h;

Steps:

25

A mixture of 4-piperidone monohydrate hydrochloride (2.5 g, 14.56 mmol) and anhydrous potassium carbonate (7 g, 50.64 mmol) in dry DMF (25 mL) was stirred for 30 min at room temperature. Benzyl bromide (2 mL, 16.82 mmol) was added dropwise into the reaction mixture and heated at 65 °C for 14 h. The reaction mixture was cooled to room temperature, filtered and quenched with ice water (25 mL). The resulting mixture was extracted in ethyl acetate (2 x 20 mL) and the combined organic layers were washed with water (2 x 15 mL) followed by brine (20 mL). The organic phase obtained was dried over anhydrous sodium sulphate and evaporated. The crude product obtained was purified by crystallisation using 2 % methanol in chloroform to afford the title compound.Yield: 2.5 g (89.28 %); ¹ HNMR (CDCI₃, 300MHz): δ 7.34 (m, 4H), 7.29 (m, 1 H), 3.62 (S, 2H), 2.75 (t, 4H), 2.46 (t, 4H).

References:

WO2011/104680,2011,A1 Location in patent:Page/Page column 77-78

793-19-1 Synthesis