(1R trans)-2-(3,4-difluorophenyl)cyclopropane amine

Physical Form

Solid

Uses

(1S,2R)-2-(3,4-Difluorophenyl)-cyclopropanamine is an intermediate used to prepare ticagrelor (T437700).

Synthesis Reference(s)

Synthesis of 2-(3,4-difluorophenyl)cyclopropanamine derivatives and salts. EU Patent EP2644590A1

Synthesis

1,2-Difluorobenzene is reacted with 3-chloropropionyl chloride to produce 3-chloro-1-(3',4'-difluorophenyl)-propan-1-one, which is by addition of N,N-dimethylformamide, phloroglucinol and sodium iodide in the next step converted to 1-(3',4'-difluorophenyl)-3-nitro-propan-1-one. The keto group of the latter intermediate is in the subsequent step stereochemically reduced to hydroxyl group by the use of chiral oxazaborolidine together with borane dimethyl sulfide or borane-N,N-diethyl aniline complex in the presence of tetrahydrofurane. The obtained (1R)-1-(3',4'-difluorophenyl)-3-nitro-propan-1-ol is then added to a mixture of triphenylphosphine and diethylazodicarboxylate in benzene to yield (1S,2R)-2-(3',4'-difluorophenyl)-1-nitrocyclopropane, which is in the last step converted to 2-(3,4-difluorophenyl)cyclopropane amine by reduction of the nitro group by catalytic hydrogenation with palladium catalyst and zink dust.