- 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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- Process for preparation of intermediates of arformoterol
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An improved method for the preparation of optically pure isomers of Formoterol is disclosed, particularly the (R,R)-isomer.A method of preparation of substantially enantiomerically pure (R,R)-1-(4-Benzyloxy-3-nitro-phenyl)-2-[[2-(4-methoxy-phenyl)-1-methyl-ethyl]-(1-phenyl-ethyl)-amino]-ethanol to use in the production of (R,R)-Formoterol is also disclosedAn improved method for the preparation of optically pure isomers of Formoterol is disclosed, particularly the (R,R)-isomer. A method of preparation of substantially enantiomerically pure (R,R)-1-(4-Benzyloxy-3-nitro-phenyl)-2-[[2-(4-methoxy-phenyl)-1-methyl-ethyl]-(1-phenyl-ethyl)-amino]-ethanol to use in the production of (R,R)-Formoterol is also disclosed
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Page/Page column 9
(2011/08/07)
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- Process for the manufacturing of pharmaceutically active compounds
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A process for making a compound of formula 1 or a salt thereof, wherein: R1 and R2 are each independently H, halogen, or C1-4-alkyl, or R1 and R2 together are C1-6-alkylene; and R3 /s
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Page/Page column 11
(2008/06/13)
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- An efficient enantioselective synthesis of (R,R)-formoterol, a potent bronchodilator, using lipases
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The potent β2-adrenergic receptor agonist formoterol (R,R)-1 has been obtained in enantiomerically pure form by a convenient chemoenzymatic approach by coupling of epoxide (R)-6 with the unprotected primary amine (R)-9. Both chiral precursors have been prepared by enantiodifferentiation processes involving Pseudomonas cepacia (lipase PS) and Candida antarctica lipase (CALB), respectively. For the resolution of amine 9, we have found that utilization of triethylamine as non-reactive base enhances the reaction rate and the enantioselectivity of the process. The key coupling reaction of (R)-6 and (R)-9 has been conducted through derivatization of the amine with the labile trimethylsilyl group, which liberates the amino group of the resulting amino alcohol (R,R)-11 upon column chromatography purification. In this way, the overall approach is shorter than others previously described. Copyright (C) 2000 Elsevier Science Ltd.
- Campos, Francisco,Bosch, M. Pilar,Guerrero, Angel
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p. 2705 - 2717
(2007/10/03)
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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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