Patent ID: 6492555
Filing Date: 2002-12-10
Classification: C07B,C07C,C07D

Abstract:
A process for the production of an (S)-Roxa-RINGâ€”CH2â€”NHâ€”COâ€”RN of the formula (X)Roxa-RINGâ€”CH2â€”NHâ€”COâ€”RNâ€ƒâ€ƒ(X) where RING means:(I) RN is C1-C5 alkyl; (II) Roxa is phenyl substituted with one â€”F and one substituted amino group which comprises: (1) contacting a carbamate of the formula (IX) Roxaâ€”NHâ€”COâ€”Oâ€”X1â€ƒâ€ƒ(IX) where:(I) X1 is (A) C1-C20 alkyl, (B) C3-C7 cycloalkyl, (C) &phgr;- optionally substituted with one or two: (1) C1-C3 alkyl, (2) Fâ€”, Clâ€”, Brâ€”, Iâ€”, (D) CH2&boxH;CHâ€”CH2â€”, (E) CH3â€”CH&boxH;CHâ€”CH2â€”, (F) (CH3)2C&boxH;CHâ€”CH2â€”, (G) CH2&boxH;CHâ€”, (H) &phgr;-CH&boxH;CHâ€”CH2â€”, (I) &phgr;-CH2â€” optionally substituted on &phgr;- with one or two â€”Cl, C1-C4 alkyl, â€”NO2, â€”CN, â€”CF3, (J) 9-fluorenylmethyl, (K) (Cl)3Câ€”CH2â€”, (L) 2-trimethylsilylethyl, (M) &phgr;-CH2â€”CH2â€”, (N) 1-adamantyl, (O) (&phgr;)2CHâ€”, (P) CHCâ‰¡Câ€”C(CH3)2â€”(Q) 2-furanylmethyl, (R) isobornyl, (S) â€”H; (II) Roxa is as defined above; with a compound selected from the group consisting of a (S)-protected alcohol of the formula (IVA) X2â€”CH2â€”C*H(OH)â€”CH2â€”N&boxH;CHâ€”X0â€ƒâ€ƒ(IVA) where:(I) X0 is: (A) -&phgr;, (B) o-hydroxyphenyl, (C) o-methoxyphenyl, (D) p-methoxyphenyl; (II) X2 is: (A) â€”Cl, (B) â€”Br, (C) p-CH3-&phgr;-SO2â€”, (D) m-NO2-&phgr;-SO2â€”; and a (S)-3-carbon protected epoxide of the formula (IVB)â€”O#â€”CH2â€”C*#Hâ€”CH2â€”N&boxH;CHâ€”X0â€ƒâ€ƒ(IVB) where:(I) # indicates that the atoms marked with a (#) are bonded to each other resulting in the formation of a ring, (II) X0 is as defined above in the presence of a lithium cation and a base whose conjugate acid has a pKa of greater than about 8 to produce a (S)-protected oxazolidinone of the formula (XII) Roxa-RINGâ€”CH2â€”N&boxH;CHâ€”X0â€ƒâ€ƒ(XII) where X0 and Roxa are as defined above;(2) contacting the reaction mixture of step (1) with aqueous acid to produce an (S)-oxazolidinone free amine of the formula (XIII) and Roxa-RINGâ€”CH2â€”NH2â€ƒâ€ƒ(XIII) (3) contacting the product of step (2) with an acylating agent selected from the group consisting of an acid anhydride of the formula O(COâ€”RN)2 where RN is as defined above or an acid halide of the formula RNâ€”COâ€”X4 where X4 is â€”Cl or â€”Br and where RN is as defined above and a tri(alkyl)amine where alkyl is C1-C5 where Roxa is as defined above.