- Method for synthesizing arformoterol free alkali
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The invention discloses a method for synthesizing arformoterol free alkali, which comprises the following steps of: (1) performing carbonyl chiral reduction reaction on a compound shown as a formula SM1 serving as a raw material in a first solvent to obtain a reaction solution containing a compound shown as a formula M1, and concentrating to dryness; (2) dissolving the material obtained in the step (1) with a second solvent, carrying out a hydrogenation reaction to obtain a reaction liquid containing a compound represented by a formula M2, filtering the reaction liquid, and cooling the filtrate; (3) carrying out formylation reaction on the filtrate cooled in the step (2) to obtain a reaction solution containing a compound as shown in a formula M3, and concentrating to dryness; (4) dissolving the material obtained in the step (3) with a third solvent, carrying out a cyclization reaction to obtain a reaction liquid containing a compound represented by a formula M4 and free SM2, filtering, and concentrating the filtrate to dryness; and (5) dissolving the material obtained in the step (4) with a fourth solvent, carrying out a condensation reaction to obtain an arformoterol precursor represented by a formula M5, and carrying out hydrogenation debenzylation on the M5 to obtain arformoterol.
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Paragraph 0063; 0068; 0070; 0075; 0077; 0082
(2021/01/30)
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- PROCESS FOR THE PREPARATION OF ARFORMOTEROL OR SALT THEREOF
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Provided is an improved process for the preparation of arformoterol L-(+)-tartrate, and more specifically provided is a novel process for the preparation of arformoterol L-(+)-tartrate via arformoterol D-(?)-tartrate.
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- PROCESSES FOR PREPARING SUBSTANTIALLY PURE ARFORMOTEROL AND ITS INTERMEDIATES
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Provided herein are improved, convenient and industrially advantageous processes for the preparation of N-[2-hydroxy-5-[(1R)-1-hydroxy-2-[[(1R)-2-(4-methoxyphenyl)-1-methylethyl]amino]ethyl]phenyl]formamide (Arformoterol) or a pharmaceutically acceptable salt thereof, in high yield and purity. Provided further herein is an improved and industrially advantageous process for the preparation of a substantially enantiomerically pure arformoterol intermediate, (R)-4-methoxy-α-methyl-N-(phenylmethyl)benzeneethanamine.
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Page/Page column 113
(2012/01/13)
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- PROCESS FOR THE SYNTHESIS OF ARFORMOTEROL
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The present invention provides a process for preparing a compound of formula (Vl) 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 (Vl), 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.
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Page/Page column 35
(2009/12/28)
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- Enantio- and diastereoselective synthesis of all four stereoisomers of formoterol
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Enantioselective syntheses of all four stereoisomers of formoterol are accomplished using asymmetric catalytic borane reductions with chiral oxazaborolidines as reducing agents.
- Hett, Robert,Fang, Qun Kevin,Gao, Yun,Hong, Yaping,Butler, Hal T.,Nie, Xiaoyi,Wald, Stephen A.
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p. 1125 - 1128
(2007/10/03)
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