preparation of (1s, 2r)-2-phenyl-cyclopropylamine hydrochloride_kain industrial additive

background and overview^[1]

(1s, 2r)-2-phenyl-cyclopropylamine hydrochloride can be used as a pharmaceutical synthesis intermediate. if (1s, 2r)-2-phenyl-cyclopropylamine hydrochloride is inhaled, move the patient to fresh air; if skin contact occurs, remove contaminated clothing and wash skin thoroughly with soap and water, if any if you feel discomfort, seek medical attention; if eye contact occurs, separate eyelids, rinse with running water or saline, and seek medical attention immediately; if ingested, rinse mouth immediately, do not induce vomiting, and seek medical attention immediately.

preparation^[1]

the preparation of (1s, 2r)-2-phenyl-cyclopropylamine hydrochloride is divided into the following steps:

step 1: general procedure for the synthesis of trans and cis 2-phenylcyclopropylcarboxylic acids (4a-c and 5a-c). example: trans 2-(4-nitrophenyl)cyclopropylcarboxylic acid (4c). a solution of 2c (9.95 mmol, 2.34 g) and 2nkoh (19.9 mmol, 1.12 g) in ethanol (30 ml) was stirred at room temperature overnight. the reaction was quenched by adding 2 n hcl until ph = 2, then the precipitate was filtered, washed with water (3 × 30 ml) and dried to give pure 4c as a light yellow solid. compound 4a. the yield is 93%. melting point: 93-95℃

step 2: general/typical procedure: general procedure for the synthesis of trans and cis tert-butyl 2-(4-nitrophenyl)cyclopropylcarbamate (6a-c and 7a-c). example: trans-tert-butyl 2-(4-nitrophenyl)cyclopropylcarbamate (6c). 4c (5.3 mmol, 1.1 g) was dissolved in anhydrous benzene (20 ml), triethylamine (6.4 mmol, 0.9 ml), diphenylphosphoryl azide (5.8 mmol; 1.2 ml) and tert-butanol (53 mmol, the solution in 5 ml) was stirred under nitrogen atmosphere and kept at 80 °c for 16 h. then, di-tert-butyl dicarbonate (8 mmol, 1.7 g) was added, and the reaction was continued at 80°c for 2 hours. the solvent was removed in vacuo, and the residue was purified by silica gel chromatography, eluting with ethyl acetate/n-hexane 1/3, to obtain pure 6c as a pale yellow solid. compound 6a. the yield is 58%. melting point: 78-80℃

step 3: synthesis of (±)-tpcpa, (±)-cpcpa, (±)-br-tpcpa and (±)-br-tpcpa from trans-2-(4-aroyl (or arylacetyl or benzyloxycarbonyl) general procedure for ±)-br-cpcpa hydrochloride) aminophenyl) cyclopropylamine hydrochloride (13a-h), trans 4-(n-benzyloxycarbonylaminoacyl) aminophenyl) cyclopropylamine hydrochloride salts (14a-m, 18 and 20), and cis-tert-butyl 2-[4-(n-)benzyloxycarbonylphenylalanyl)aminophenyl]cyclopropylamine hydrochloride (15). example: trans 2-[4-(n-benzyloxycarbonyltryptophanyl)aminophenyl]cyclopropylamine hydrochloride (14l). a solution of 6nhcl (2 ml) was added to a solution of 11 l (0.26 mmol, 0.1 g) in tetrahydrofuran (2 ml) and the mixture was stirred at room temperature for 12 hours. the precipitated solid was filtered, washed with diethyl ether (3 x 10 ml) and dried to give pure 14l as a colorless solid. (±)-tpcpa; (±)-cpcpa.

step 4: general synthesis of (±)-tpcpa, (±)-cpcpa, (±)-br-tpcpa and (±)-br-cpcpa hydrochloride from trans 2-(4-aroyl) procedure (or arylacetyl or benzyloxycarbonyl)aminophenyl)cyclopropylamine hydrochloride (13a-h), trans 4-(n-benzyloxycarbonylaminoacyl)aminophenyl)cyclopropylamine hydrochloride salts (14a-m, 18 and 20), and cis-tert-butyl 2-[4-(n-benzyloxycarbonylphenylalanyl)aminophenyl]cyclopropylamine hydrochloride (15). example: trans 2-[4-(n-benzyloxycarbonyltryptophanyl)aminophenyl]cyclopropylamine hydrochloride (14l). a solution of 6nhcl (2 ml) was added to a solution of 11 l (0.26 mmol, 0.1 g) in tetrahydrofuran (2 ml) and the mixture was stirred at room temperature for 12 hours. the precipitated solid was filtered, washed with diethyl ether (3 × 10 ml) and dried to obtain pure (1s, 2r)-2-phenyl-cyclopropylamine hydrochloride as a colorless solid. (±)-tpcpa; (±)-cpcpa. the yield is 95%. melting point: 162-164℃

main reference materials

[1] biochemical, structural, and biological evaluation of tranylcypromine derivatives as inhibitors of histone demethylases lsd1 and lsd2