Process for the Synthesis of Arformoterol

摘要

The present invention provides a process for preparing a compound of formula (VI) or a salt thereof, the process comprising: (i) reacting 4-methoxyphenyl acetone with an amine of formula (VIII) under conditions of reductive amination to produce a compound of formula (II) or a salt thereof, wherein there is no isolation of an imine intermediate formed during the reductive amination; (ii) condensing the compound (II) or the acid addition salt thereof with an α-haloketone of formula (III) to produce the compound of formula (IV); (iii) reducing the compound (IV) to a compound of formula (V); and (iv) reducing the compound (V) to the compound of formula (VI), wherein the reduction is carried out in the presence of either (1) a hydrogen donating compound in the presence of a hydrogen transfer catalyst; or (2) ammonium formate using a hydrogenation catalyst, wherein R1 and R2 are independently optionally substituted arylalkyl, and Hal is selected from chloro or bromo.;

主权项

1. A process for preparing the (R,R)-diastereromer of a compound of formula (VI) or a salt thereofthe process comprising (i) reacting 4-methoxyphenyl acetone with an amine of formula (VIII) under conditions of reductive amination to produce a compound of formula (II) or a salt thereof, wherein there is no isolation of an imine intermediate formed during the reductive amination,(ii) condensing the (R)-enantiomer of compound (II) or the acid addition salt thereof with an α-haloketone of formula (III) to produce the (R)-enantiomer of a compound of formula (IV)(iii) reducing the (R)-enantiomer of compound (IV) to the (R,R)-diastereomer of a compound of formula (V)and (iv) reducing the (R,R)-diastereomer of compound (V) to the (R,R)-diastereomer of the compound of formula (VI), wherein the reduction is carried out by either (1) a hydrogen donating compound in the presence of a hydrogen transfer catalyst or (2) ammonium formate using a hydrogenation catalyst, wherein R1 and R2 are independently optionally substituted arylalkyl, and Hal is selected from chloro or bromo.