1-(3-fluorophenyl)cyclopropanamine hydrochloride synthesis

Yield:692737-66-9 26.5%

Reaction Conditions:

Stage #1: 1-(3-fluorophenyl)cyclopropane-1-carboxylic acidwith diphenyl phosphoryl azide;triethylamine in tert-butyl alcohol at 80; for 27 h;
Stage #2: with hydrogenchloride in 1,4-dioxane at 20; for 1 h;

Steps:

3-1 Example 3-1

Compound 1-(3-fluorophenyl)cyclopropane-1-carboxylic acid (5 g, 27.75 mmol),Triethylamine (7.02g, 69.375mmol)Dissolved in tert-butanol (50ml),Diphenylphosphoryl azide (9.55 g, 34.69 mmol) was added,Stir at room temperature for 3 hours,It was then heated to 80°C and stirred for 24 hours.After cooling, the reaction was quenched with water,And extract with the solvent of ethyl acetate: petroleum ether=1:10,The combined organic phases were concentrated, and the concentrate was dissolved in a 6M solution of hydrochloric acid (30 ml).Heating to 80°C was continued with stirring overnight.After the reaction was completed, it was cooled to room temperature and diluted with water,Extract with ethyl acetate:petroleum ether=1:10 solvent, adjust the pH value of the aqueous phase to 8-9, then extract with ethyl acetate, combine the organic phases and dry with anhydrous sodium sulfate,The crude product obtained by concentration was dissolved in 4M hydrochloric acid/1,4-dioxane solution,Stir at room temperature for 1 hour,The reaction solution was concentrated, ethyl acetate was added,Filtration to obtain compound 1-(3-fluorophenyl)cyclopropan-1-amine hydrochloride (1.38g), yield 26.5%,

References:

CN113861072,2021,A Location in patent:Paragraph 0154-0158