Preparation method of 2-(methyl sulphonyl)-1-aromatic ethylamine

A technology of arylethylamine and methylsulfonyl, applied in the field of pharmaceutical chemical synthesis, can solve the problems of inconvenient production, high risk and high equipment requirements

Inactive Publication Date: 2017-04-26
HANGZHOU XINBOSI BIOMEDICAL CO LTD
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  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0008] In order to overcome the defects of the prior art, the object of the present invention is to provide a new preparation process of 2-(methylsulfonyl)-1-arylethylamine, which solves the inconvenience of production, high equipment requirements and risky High, high cost issues

Method used

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  • Preparation method of 2-(methyl sulphonyl)-1-aromatic ethylamine
  • Preparation method of 2-(methyl sulphonyl)-1-aromatic ethylamine

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0013] Embodiment 1: the synthetic technique of 2-(methylsulfonyl)-1-phenylethylamine

[0014] Add 60 ml of methanol, 13.0 g of 2-(methylsulfonyl) acetic acid and 18.2 g of ammonium acetate into a 500 ml three-necked flask, heat to 45°C, add 10.2 g of benzaldehyde dropwise, and heat to reflux after dropping. Cool to below 10°C, add 34.0 g of thionyl chloride dropwise, after the drop is complete, heat to reflux for 17 h, and distill off the methanol. Add 50 ml of dichloromethane to the residue, and adjust the pH to 6~7 with 5 mol / L NaOH solution. The organic layer was separated, and the aqueous layer was extracted with dichloromethane. The organic layers were combined and concentrated to obtain 10.3 g of a colorless oil, with a HPLC purity of 98% and a yield of 61%. 1H NMR (DMSO-d6) δ 1.32 (t, J=7.0 Hz, 3H), 2.08 (s, 2H), 2.96 (s,3H), 3.23 (dd, J=3.6, 14.4 Hz, 1H), 3.41 ( dd, J=9.4, 14.4 Hz, 1H), 3.73 (s,3H), 4.02 (q, J=7.0 Hz, 2H), 4.26 (dd, J=3.7, 9.3 Hz, 1H), 6.89 (s, 2H ...

Embodiment 2

[0015] Embodiment 2: the synthesis technique of 1-(3-ethoxy-4-methoxyphenyl)-2-(methylsulfonyl)ethylamine

[0016] Add 50 ml of ethanol, 12.4 g of 2-(methylsulfonyl) acetic acid and 18.2 g of ammonium acetate to a 500 ml three-necked flask, heat to 50 °C, add 10.0 g of 3-ethoxy-4-methoxybenzaldehyde dropwise, After dropping, heat to reflux for reaction. Cool to below 10°C, add 40 g of thionyl chloride dropwise, heat to reflux for 16 hours, and distill off ethanol. Add 50 ml of dichloromethane to the residue, and adjust the pH to 6~7 with 5 mol / L NaOH solution. The organic layer was separated, and the aqueous layer was extracted with dichloromethane. The organic layers were combined and concentrated to give 14.2 g of a colorless oil, with a HPLC purity of 98%, and a yield of 78%. 1 H NMR (DMSO- d 6 ) δ 1.32 (t, J =7.0 Hz, 3H), 2.08 (s,2H), 2.96 (s, 3H), 3.23 (dd, J =3.6, 14.4 Hz, 1H), 3.41 (dd, J =9.4, 14.4 Hz,1H), 3.73 (s, 3H), 4.02 (q, J =7.0 Hz, 2H), 4.26 (dd, J =3...

Embodiment 3

[0017] Embodiment 3: the synthesis technique of 1-(3-trifluoromethylphenyl)-2-(methylsulfonyl)ethylamine

[0018] Add 75 ml of methanol, 13.0 g of 2-(methylsulfonyl) acetic acid and 10.9 g of ammonium acetate to a 500 ml three-necked flask, heat to 50 °C, add 10.0 g of 3-trifluoromethylbenzaldehyde dropwise, and heat to reflux reaction. Cool to 0~5°C, add 55 g of thionyl chloride dropwise, heat to reflux for 17 h, and distill off methanol. 50ml of dichloromethane was added to the residue, and the pH was adjusted to 6~7 with 5N NaOH solution. The organic layer was separated, and the aqueous layer was extracted with dichloromethane. The organic layers were combined and concentrated to give 9.8 g of a colorless oil, HPLC purity 98%, yield 58%, 1H-NMR (400 MHz, DMSO-d6): δ = 3.01 (s, 3H), 3.84 (dd, 1H) , 4.03 (dd,1H), 5.01 (t, 1H), 7.71 (t, 1H), 7.82 (d, 1H), 7.91 (d, 1H), 8.03 (s, 1H),8.75 (br. s., 3H).

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Abstract

The invention provides a novel preparation method of 2-(methyl sulphonyl)-1-aromatic ethylamine as shown in a formula (II) defined in the description. The method comprises the step that R substituted benzaldehyde, 2-(methyl sulphonyl)acetic acid and ammonium acetate which are as shown in a formula (I) defined in the description serve as raw materials to synthesize 2-(methyl sulphonyl)-1-aromatic ethylamine as shown in the formula (II) defined in the description. By means of the method, the defects that similar products are high in production cost, strict in condition, low in yield and the like are overcome, and great application value and economic benefit are achieved.

Description

technical field [0001] The invention relates to the field of pharmaceutical chemical synthesis, in particular to a preparation method of 2-(methylsulfonyl)-1-arylethylamine. Background technique [0002] Arylethylamine is an important intermediate in organic synthesis and pharmaceutical industry. Among them, the well-known important intermediate 1-(3-ethoxy-4-methoxyphenyl)-2 of apremilast, the first small molecule drug approved for the treatment of adult patients with active psoriatic arthritis -(Methylsulfonyl)ethylamine is one such drug. At present, the demand for arylethylamine products in domestic and foreign markets is relatively large, and the demand is increasing, and the price is high. However, the production of such products has the disadvantages of high cost, harsh production conditions, and low yield. Therefore, it will be of great research value and economic benefit to develop a new synthetic route of arylethylamine suitable for industrialization. This paper...

Claims

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Application Information

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IPC IPC(8): C07C315/04C07C317/28
CPCC07C315/04
Inventor 刘国民刘艳华毛景雯
Owner HANGZHOU XINBOSI BIOMEDICAL CO LTD
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