Patent GB-762357-A (GB)
Title: Trans-4-carbalkoxy-5-(ú­-nitrophenyl) oxazolines
IPC: C07D263/16
Filed: 1953-04-07
Abstract: A process for preparing trans-4-carbalkoxy-5-(para-nitrophenyl) oxazolines of formula <FORM:0762357/IV(b)/1> wherein R1 is a (C1-C4) alkyl group and R2 is a methyl, dichloromethyl or phenyl group, comprises forming a DL-threo-b -(paranitrophenyl) alkyl serinate of formula <FORM:0762357/IV(b)/2> (1) by reacting para-nitrobenzaldehyde with an alkyl glycine NH2-CH2-COOR1 and with a compound HX selected from phenol, aniline, alkyl malonates and (C1-C4) alkyl glycine (e.g. an excess of the first alkyl glycine), either in one stage or in two stages whereby the intermediate N - (a  - hydroxy - para - nitrobenzyl) alkyl glycine of formula <FORM:0762357/IV(b)/3> formed by reacting glycine and para-nitrobenzaldehyde in stoichiometric proportions, is separated and then reacted with HX; (2) by reacting at least one mol. of an alkyl glycine NH2-CH2-COOR1 with a compound of formula <FORM:0762357/IV(b)/4> wherein Y is <FORM:0762357/IV(b)/5> formed by reacting para-nitrobenzaldehyde and a compound HY; and (3) by racemizing with an alkyl glycine a D-threo-b -(para-nitrophenyl) (C1-C4) alkyl serinate obtained by resolving the DL-form with lactic acid in a later stage of the process; and condensing the alkyl serinate prepared by the above methods (or an enantiomorph thereof obtained by resolving the racemic form with D- or L-lactic acid) with an imino-ether of formula <FORM:0762357/IV(b)/6> Reactions (1)-(3) are preferably conducted in a solvent such as ether, dioxan, benzene or ethanol.  When HY in method (2) is an N-(para-nitrobenzylidene) (C1-C4) alkyl glycine, the erythro form is preferably used.  The iminoether condensation is preferably conducted at 15-30 DEG  in a solvent such as dioxan, chloroform or ethyl acetate, one or both reactants being used in the form of a salt and excess of imino-ether being used as an acid binding agent.  The D- and L-lactic acid used to resolve the DL - threo - b  - (para - nitrophenyl) alkyl serinate may be replaced by DL-lactic acid enriched in D- or L-lactic acid. The racemate may be separated into D- and L-enantiomorphs by alternate treatment with D- and L-enriched lactic acid, fresh racemate being added to the mother liquor to make up for each quantity of enantiomorphs removed.  The lactates may be used directly in the final stage of process or may be first converted to other salts (e.g. hydrochloride) or to the free serinates.  The examples describe the preparation of DL- and L(-) - trans - 2 - phenyl - 4 - carbethoxy - 5-(para - nitrophenyl) - oxazolines, DL - and L(+) - trans - 2 - dichloromethyl - 4 - carbethoxy-5 - (para - nitrophenyl) - oxazolines, DL - trans-2 - methyl - 4 - carbethoxy - 5 - (para - nitrophenyl) - oxazoline, DL - trans - 2 - dichloromethyl - 4 - carbomethoxy - 5 - (para - nitrophenyl) - oxazoline and DL - trans - 2 - phenyl-4 - carbomethoxy - 5 - (para - nitrophenyl)-oxazoline. The preparation of the following intermediates is also described:  DL - threo - b  - (para - nitrophenyl) methyl serinate, D -, L - and DL - threo - b  - (para-nitrophenyl) ethyl serinates and hydrochlorides thereof, the L-lactate of D-threo-b -(para-nitrophenyl) ethylserinate, the D-lactate of L-threo-b -(para-nitrophenyl) ethyl serinate, N-(para-nitrobenzylidene) ethyl glycine, N-(a -hydroxy-para-nitrobenzyl) ethyl glycine and erythro-N-(para-nitrobenzylidene) - b  - (para - nitrophenyl) ethyl serinate.  Specification 728,704 is referred to.