ChemicalBook CAS DataBase List Nefopam hydrochloride

Nefopam hydrochloride synthesis

8synthesis methods

Product Name:Nefopam hydrochloride
CAS Number:23327-57-3
Molecular formula:C17H20ClNO
Molecular Weight:289.8

The method for a synthetic hydrochloric acid nefopam; Comprise: with o-benzoylbenzoic acid (BB acid) is main raw material; Successively through acyl chloride reaction, amination reaction, chlorination reaction, reductive hydrolysis reaction, ring-closure reaction and neutralization reaction; Final refining obtains nefopam hydrochloride.

Benzenemethanol, 2-[(methylamino)methyl]-α-phenyl-, hydrochloride (1:1)

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79-04-9 Synthesis

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Yield:23327-57-3 65%

Reaction Conditions:

Stage #1:1-((2-(methylamino)methyl)phenyl)-1-phenylmethanol hydrochloride;chloroacetyl chloride with triethylamine in dichloromethane at 25; for 2 h;Inert atmosphere;
Stage #2: with sodium tetrahydroborate;potassium tert-butylate;isopropyl alcohol in dichloromethane; pH=6.5 at 20; for 19 h;

Steps:

3) The preparation route of Nefopam hydrochloride
Intermediate 1-((2-(methylamino)methyl)phenyl)-1-phenylmethanol hydrochloride (14.5 g, 0.055 mol),Dichloromethane (200 mL),Triethylamine (14.0 g, 0.14 mol) was added to the nitrogen protected reaction system.Reduce the temperature to 0 °C,A solution of chloroacetyl chloride (7 g, 0.06 mmol) in DCM (50 mL) was slowly added dropwise. After completion of the addition, the reaction was continued for 2 h and the temperature was raised to 25 °C.Add isopropyl alcohol (150 mL),Potassium tert-butoxide (6.8g, 0.06mol)Isopropanol (50mL)The solution was slowly added dropwise to the reaction system.After the addition, the reaction was completed for 1 h, and the pH was adjusted to about 6.5 with glacial acetic acid.Sodium borohydride (6.3 g, 0.165 mol) was added,Stir at room temperature for 18h, slowly add ice water, stir for 30min, layer,The organic layer is flushed with hydrochloric acid to a pH of about 1,Hydrochloric acid gas was stopped and the mixture was filtered. The filter cake was washed with a mixture of isopropyl alcohol and dichloromethane (volume ratio of 1:1) and dried to obtain 10.4 g of the target compound in a yield of 65%

References:

Kangpu Pharmaceutical Co., Ltd.;Zhang Chunsheng;Liu Da;Wu Jianmin;Zhang Jing CN107556263, 2018, A Location in patent:Paragraph 0018; 0023

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