Process for the synthesis of morpholinylbenzenes
AssigneeAstraZeneca AB
InventorWei Tian
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Abstract
A new improved process for synthesizing morpholinylbenzenes of the formula I by reacting morpholine of II with a substituted benzene of formula III, wherein morpholine is used as a reactant and as the only one solvent. 1
Claims17
An improved process for synthesizing 4-morpholinylbenzene of the formula I
- 5
- by reacting morpholine of formula II with a substituted benzene of formula III,
- 6
- wherein
- Y and Y1 are a substituent in 2- or 4-position and
- Y is Y1 or COOH,
- Y1 is CN, NO2, CF3, COOR1, COR1, CONR2R3
- where R1 is H, C1-6 alkyl, C3-6 cycloalkyl, C1-3 alkylC3-6 cycloalkyl, C6-C10 aryl or a heterocyclic ring containing one or two heteroatoms selected from N, O, S, and said heterocyclic ring may optionally be substituted;
- where R2, R3 is H, C1-6 alkyl, C3-6 cycloalkyl, C1-3 alkylC3-6 cycloalkyl and C6-C10 aryl or a heterocyclic ring containing one or two heteroatoms selected from N, O, S, and said heterocyclic ring may optionally be substituted, or may together with the nitrogen atom form a heterocyclic ring;
- with the provisio that Y, is not COOH,
- X is a leaving group,
- characterized in that the morpholine is used as reactant and the only one solvent, if solvent is present,
- and, if necessary, hydrolysis to form a compound wherein Y is COOH.
A process according to any one of the proceeding claims, wherein the substituent Y and Y1 is in the 4-position.
A process according to any one of the proceeding claims, wherein the molar ratio of the reactant morpholine to substituted benzene ranges preferably in the ranges from 6,7:1 to 1:1, more preferably from 3.5:1 to 1:1.
A process according to any one of the proceeding claims performed in absence of an additional base.
A process according to any one of the proceeding claims performed in the absence of a catalyst.
A process according to any one of the proceeding claims, wherein the process is performed under normal pressure and at a temperature range from 20° C. to 130° C.
Dependencies are inferred from the claim text.