188690-82-6Relevant articles and documents
An efficient enantioselective synthesis of (R,R)-formoterol, a potent bronchodilator, using lipases
Campos, Francisco,Bosch, M. Pilar,Guerrero, Angel
, p. 2705 - 2717 (2000)
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.
Diethylanilineborane: A practical, safe, and consistent-quality borane source for the large-scale enantioselective reduction of a ketone intermediate in the synthesis of (R,R)-formoterol
Wilkinson, H. Scott,Tanoury, Gerald J.,Wald, Stephen A.,Senanayake, Chris H.
, p. 146 - 148 (2002)
The development of a process for the use of N,N-diethylaniline - borane (DEANB) as a borane source for the enantioselective preparation of a key intermediate in the synthesis of (R,R)-formoterol L-tartrate, bromohydrin 2, from ketone 3 on kilogram scale is described. DEANB was found to be a more practical, safer, and higher-quality reagent when compared to other more conventional borane sources: borane - THF and borane - DMS.
Preparation method of formoterol key intermediate
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Paragraph 0080-0091; 0104; 0106; 0107, (2020/01/12)
The invention provides a preparation method of a formoterol key intermediate (R)-N-(2-(benzyloxy)-5-(2-bromo-1-hydroxyethyl)phenyl)formamide represented by a formula I, wherein asymmetric reduction isperformed by using 1-(4-(benzyloxy)-3-nitrophenyl)-2-bromoethanone (II) as a raw material and using (3aS-cis)-(-)-3,3a,8,8a-tetrahydro-2H-indeno[1,2-d]oxazole-2-isopropylborane (IV) as a catalyst toobtain a chiral alcohol intermediate (R)-1-(4-(benzyloxy)-3-nitrophenyl)-2-bromoethanol (III) with high enantioselectivity, and then nitro reduction and formylation one-pot reaction are performed to obtain a target product represented by the formula I. Compared with the traditional resolution method, the method of the invention has advantages of high chiral purity of the product, short productionperiod, easy operation, mild condition, convenient post-treatment and high yield, and is suitable for large-scale industrial production.
(S) or (R)-diphenyl-pyrrolidine methanol immobilized by pentaerythritol and its preparation method and application
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Paragraph 0019; 0020; 0022, (2018/03/28)
The invention discloses a (S/R)-diphenyl-pyrrolidine methanol immobilized by pentaerythritol and its preparation method and application. The (S/R)-diphenyl-pyrrolidine methanol is shown as Formula (I). The preparation of the catalyst includes steps of reacting pentaerythritol with paratoluensulfonyl chloride to obtain pentaerythritol sulphonate; reacting with sodium azide to obtain pentaerythritecompound; reacting (S/R)-N-Cbz-4-hydroxyproline methyl ester with propargyl bromide to obtain (S/R)-N-Cbz-4-acetylene methoxy proline methyl ester; then reacting with chlorophenylmagnesium to obtain (S/R)-diphenyl-pyrrolidine methanol immobilized by pentaerythritol. The (S/R)-diphenyl-pyrrolidine methanol immobilized by pentaerythritol can be applied to the reaction of asymmetrical transformationand generation of prochiral phenyl ketones to be (R/S)- secondary alcohol; the catalyst can be recycled.
