The Production Process of 1-(4-phenethylpiperazin-1-yl)-2-(1-phenylcyclohexyl)ethanone ascorbate

The Production Process of 1-(4-phenethylpiperazin-1-yl)-2-(1-phenylcyclohexyl)ethanone Ascorbate

1. Introduction

1-(4-Phenethylpiperazin-1-yl)-2-(1-phenylcyclohexyl)ethanone ascorbate is an important intermediate in the synthesis of some pharmaceuticals and fine chemicals.
In this article, we will discuss the production process of this compound, which involves several steps, including synthesis, purification, and characterization.

2. Synthesis of 1-(4-Phenethylpiperazin-1-yl)-2-(1-phenylcyclohexyl)ethanone

The synthesis of 1-(4-phenethylpiperazin-1-yl)-2-(1-phenylcyclohexyl)ethanone involves several steps, including the protection of the hydroxy group, the condensation reaction, and the deprotection step.
Here is a general synthesis route for this compound:

Step 1: Preparation of 4-phenethylpiperazine

To a solution of phenylalanine (10 g, 64.
8 mmol) in THF (100 mL), a solution of lithium hydroxide (2.
5 g, 64.
8 mmol) in water (50 mL) was added, and the mixture was stirred at room temperature for 30 minutes.
The reaction was quenched by the addition of MeOH (50 mL), and the mixture was filtered to remove the precipitated LiCl.
The filtrate was concentrated under reduced pressure, and the resulting residue was purified by column chromatography (eluent: CH2Cl2/MeOH = 9/1) to yield 4-phenethylpiperazine (8.
5 g, 56.
8 mmol, 87.
5% yield).

Step 2: Preparation of 1-(4-phenethylpiperazin-1-yl)-2-(1-phenylcyclohexyl)ethanone

To a solution of 1-(4-phenethylpiperazin-1-yl)-2- (1-phenylcyclohexyl)ethanone hydrochloride (2.
0 g, 5.
6 mmol) in DMF (50 mL), a solution of 2- (1- phenylcyclohexyl)acetic acid (1.
5 g, 6.
4 mmol) in DMF (25 mL) was added, and the mixture was stirred at room temperature for 24 hours.
The reaction was quenched by the addition of water (50 mL), and the mixture was extracted with EtOAc (3 x 50 mL).
The organic layer was separated, dried over Na2SO4, filtered, and concentrated under reduced pressure to yield a crude product, which was purified by column chromatography (eluent: CH2Cl2/MeOH = 9/1) to yield 1-(4-phenethylpiperazin-1-yl)-2-(1-phenylcyclohexyl)ethanone (1.
7 g, 3.
3 mmol, 56.
1% yield).

Step 3: Preparation of 1-(4-Phenethylpiperazin-1-yl)-2-(1-phenylcyclohexyl)ethanone Ascorbate

To a solution of 1-(4-phenethylpiperazin-1-yl)-2-(1-phenylcyclohexyl)ethanone (1.
0 g, 1.
7 mmol) in MeOH (50 mL), a solution of NaOAscorbate (759 mg, 2.
56 mmol) in H2O (5 mL) was added, and the mixture was stirred at room temperature for 30 minutes.
The reaction was quenched by the addition of aqueous NaOH (1 N, 5 mL), and the mixture was extracted with EtOAc (3 x 50 mL).
The organic layer was separated, dried over Na2SO4, filtered, and concentrated under reduced pressure to yield a crude product, which was purified by HPLC (eluent: