2-anilinoethanol (11) was condensed with ethyl chloroacetate in the presence of potassium tert-butoxide in tetrahydrofuran to afford the required phenylmorpholinone (12). Nitration of the intermediate morpholinone (12) in a solution of concentrated sulphuric acid with nitric acid below room temperature provided after recrystallization the para-product (13) in > 99.5% HPLC purity. The mother liquor was enriched predominantly with unwanted ortho - and meta-isomers together with depleted para-product. By subsequent hydrogenation of the nitro group in 13 with palladium on charcoal in methanol the 4-(4-Aminophenyl)morpholin-3-one (14) was obtained.
[1] W. MEDERSKI; Markus W; P Wendel.
Practical and efficient processes for the preparation of 4-(4-aminophenyl)morpholin-3-ones on a larger scale: precursor of factor Xa inhibitors[J]. Heterocycles, 2007, 74 1: 437-445. DOI:10.3987/COM-07-S(W)22.
