合成1,4-二取代-2,3,4,5-四氢-1H-3-苯并氮杂䓬的两种通用方法。

Two general routes to 1,4-disubstituted-2,3,4,5-tetrahydro- 1H-3-benzazepines.

作者信息

Gerritz S W, Smith J S, Nanthakumar S S, Uehling D E, Cobb J E

机构信息

Glaxo Wellcome, Inc., Five Moore Drive, P.O. Box 13398, Research Triangle Park, North Carolina 27709, USA.

出版信息

Org Lett. 2000 Dec 14;2(25):4099-102. doi: 10.1021/ol0067641.

DOI:10.1021/ol0067641

PMID:11112653

Abstract

[structure] Two general routes to 1,4-disubstituted-2,3,4, 5-tetrahydro-1H-3-benzazepines are described. Both routes utilize an appropriately functionalized phenethylamino alcohol as the penultimate intermediate: the first route makes use of the reductive amination of a benzyl alkyl ketone with alpha-(aminomethyl)benzyl alcohol, while the second route utilizes the addition of a Grignard reagent to the oxazolidine derived from a substitued phenylacetaldehyde and alpha-(methylaminomethyl)benzyl alcohol. In all cases studied, the cis-1,4-disubstituted-2,3,4, 5-tetrahydro-1H-3-benzazepine was obtained as the major product.

摘要

[结构] 本文描述了两种合成1,4-二取代-2,3,4,5-四氢-1H-3-苯并氮杂䓬的通用方法。两种方法均使用适当官能化的苯乙胺醇作为倒数第二个中间体：第一种方法利用苄基烷基酮与α-(氨基甲基)苄醇的还原胺化反应，而第二种方法利用格氏试剂加成到由取代苯乙醛和α-(甲基氨基甲基)苄醇衍生的恶唑烷上。在所有研究的情况下，顺式-1,4-二取代-2,3,4,5-四氢-1H-3-苯并氮杂䓬均作为主要产物得到。