N-Boc-(S)-二羟甲基吗啉的合成研究

Study on synthesis of N-boc-(S)-2-(hydroxymethyl)morpholine

研究讨论了以D-甘露醇为原料,经过丙叉化反应,高碘酸钠氧化,通过引入苄胺使手性碳原子构型发生转变。接着进行氯乙酰化、醋酸脱丙叉以及碱性环境下关环反应。还原内酰胺生成(S)-N-苄基-2-羟甲基吗啉,Pd/C催化脱苄基,最后上叔丁氧羰基保护,制得标题化合物,总产率约35%。

This paper describes the synthesis in six steps of the derivations of N-Boc-（S）-2-（hydroxymethyl）morpholine in an overall yield of 35%.The optically active compounds of 4-Boc-2-hydroxymethylmorpholine were prepared from D-mannitol by practical procedures.As a frequently used chiral pool,D-mannitol has been finding extensive application in the organic synthesis.Our approach was to build the chiral morpholine moiety.Firstly,the cleavage of di-O-isopropylidene-1,2∶5,6-D-mannitol with sodium metaperiodate was realized,followed by reductive amination of O-isopropylidene-（R）-glyceraldehyde with benzylamine in the presence of sodium borohydride.Acylation with chloroacetyl chloride,and removal of the isopropylidene group in aqueous acetic acid gave the diol,which was treated with sodium ethoxide to yield the lactam.N-tert-Butoxycarbonylmorpholine was prepared through the hydride reduction of lactam,the reductive removal of the benzyl group with palladium on carbon in H2,and the subsequent tert-butoxycarbonylation with Boc-2-O-（di-tert-butyl dicarbonate）.