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Procedure for the synthesis of arformoterol
专利权人:
CIPLA LIMITED
发明人:
HALDAVANEKAR, VAMAN,PRABHU, MANGESH,RAO, DHARMARAJ,KANKAN, RAJENDRA
申请号:
ES09757755
公开号:
ES2539947T3
申请日:
2009.06.02
申请国别(地区):
ES
年份:
2015
代理人:
摘要:
A process for preparing the diastereomer (R, R) of a compound of formula (VI) or a salt thereof ** Formula ** method 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 an imine intermediate formed during the reductive amination is not isolated and where the reductive amination is performed in the presence of an ionic compound in a organic solvent or an aqueous solvent or a mixture thereof, ** Formula ** (ii) condensing the enantiomer (R) of compound (II) or the acid addition salt thereof with a -haloketone of formula (III) to produce the enantiomer (R) of a compound of formula (IV) ** Formula ** (iii) reduce the enantiomer (R) of a compound (IV) to the diastereomer (R, R) of a compound of formula (V) , wherein the compound (IV) is subjected to chiral reduction with a chiral reducing agent s selected from the group consisting of (-) - DIP-chloride, -isopinocanfinyl-9BBN (R-Alpine-borane), a chiral complex of -oxoaldiminatocobalt (II), a dioxazaluminium complex (derived from amino acid esters, LiAlH4 and methyl sulphide of borane), dihydrooxazaborinos and a borane reducing agent; in the presence of a catalytic amount of a single enantiomer of an oxazaborolidine reagent derived from a chiral oxazaborolidine catalyst, ** Formula ** and (iv) reduce the diastereomer (R, R) of the compound (V) to the diastereomer (R, R) of the compound of formula (VI), wherein the reduction is carried out in the presence of (1) a hydrogen donor compound in the presence of a hydrogen transfer catalyst or (2) ammonium formate using a hydrogenation catalyst, in where: R1 and R2 are independently optionally substituted arylalkyl and Hal is selected from chlorine and bromine.Un procedimiento para preparar el diastereómero (R,R) de un compuesto de fórmula (VI) o una sal del mismo**Fórmula** procedimiento que comprende: (i) hacer reaccionar 4-metoxifenil acetona c
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