Patent ID: 6716980
Filing Date: 2004-04-06
Classification: C07B,C07C,C07D

Abstract:
A process for the production of an (S)-Roxa-RING-CH2â€”NHâ€”COâ€”RN of the formula (X)Roxa-RING-CH2â€”NHâ€”COâ€”RN â€ƒâ€ƒ(X) where:(I) RN is C1-C5 alkyl; (II) Roxa is phenyl substituted with one -F and one substituted amino group which comprises: (III) RING means (1) contacting a carbamate of the formula (IX) Roxa-NHâ€”COâ€”Oâ€”CH2â€”X1 â€ƒâ€ƒ(IX) where:(1) X1 is: (A) C1-C20 alkyl, (B) C3-C7 cycloalkyl, (C) &phgr;-optionally substituted with one or two: (1) C1-C3 alkyl, (2) F-, Cl-, Br-, 1-, (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;-CH2-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) CHâ‰¡Câ€”C(CH3)2â€”(Q) 2-furanylmethyl, (R) isobornyl, (S) â€”H; (II) Roxa is as defined above, and (III) X2 is (A) â€”Cl, (B) â€”Br, (C) p-CH3-&phgr;-SO2â€”, (D) m-NO2-&phgr;-SO2, with an (S)-3-carbon amino alcohol (V) in the presence of a lithium cation and a base whose conjugate acid has a pK, of greater than about 8 to produce an (S)-oxazolidinone free amine of the formula (XIII) Roxa-RING-CH2â€”NH2 â€ƒâ€ƒ(XIII) where Roxa is as defined above, and(2) acylating the (S)-oxazolidinone free amine (XIII) 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 is â€”Cl or â€”Br and where RN is as defined above and a tri(alkyl)amine where alkyl is C1-C5.