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US 5,708,186 AGranted
Stereoselective process
OwnerPaul N. Devine, David M. Tschaen +1inventors
InventorsPaul N. Devine, David M. Tschaen, Richard M. Heid, Jr.
Life of this patent
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Abstract
This invention relates to a method for the stereoselective synthesis of a 2-aryloxycarboxylic acid using a chiral auxiliary to enhance the stereoselectivity of the alkylation of the .alpha.-halo acid with an aryloxy group.
Claims7
A process for the preparation of a compound of formula:
- ##STR42## wherein:
- * designates a stereogenic center;
- R.sup.c is:
- a chiral auxiliary except R.sup.c cannot be ##STR43## R is (a) (C.sub.1 -C.sub.6)-alkyl,
- (b) aryl, wherein aryl is defined as phenyl or naphthyl unsubstituted or substituted with one, two or three substitutents defined as R.sup.4, R.sup.5 and R.sup.6 ;
- R.sup.1, R.sup.2, R.sup.3, R.sup.4, R.sup.5 and R.sup.6 are independently:
- (a) H,
- (b) F, Cl, Br, or I,
- (c) --NO.sub.2,
- (d) --NH.sub.2,
- (e) --NH(C.sub.1 -C.sub.4)-alkyl,
- (f) --N(C.sub.1 -C.sub.4)-alkyl!.sub.2,
- (g) --SO.sub.2 NHR.sup.7,
- (h) --CF.sub.3,
- (i) (C.sub.1 -C.sub.6)-alkyl,
- (j) --OR.sup.7,
- (k) --S(O).sub.n --(C.sub.1 -C.sub.4)-alkyl,
- (l) --NHCO--(C.sub.1 -C.sub.4)-alkyl,
- (m) --NHCO--O(C.sub.1 -C.sub.4)-alkyl,
- (n) --CH.sub.2 O--(C.sub.1 -C.sub.4)-alkyl,
- (o) --O--(CH.sub.2).sub.m --OR.sup.7,
- (p) --CONR.sup.7 R.sup.12,
- (q) --COOR.sup.7, or
- (r) -phenyl;
- R.sup.4 and R.sup.5 on adjacent carbon atoms can be joined together to form a ring structure:
- ##STR44## A represents:
- (a) --Y--C(R.sup.8).dbd.C(R.sup.9)--,
- (b) --Y--C(R.sup.8).dbd.N--,
- (c) --Y--N.dbd.C(R.sup.8)--,
- (d) --Y--C(R.sup.10)(R.sup.10)!.sub.s --Y--,
- (e) --Y--C(R.sup.8)(R.sup.8)--C(R.sup.8)(R.sup.8)--,
- (f) --C(R.sup.8).dbd.C(R.sup.9)--Y--,
- (g) --N.dbd.C(R.sup.8)--Y--,
- (h) --C(R.sup.10)(R.sup.10)--C(R.sup.10)(R.sup.10)--Y--, or
- (i) --C(R.sup.8 ).dbd.C(R.sup.9)--C(R.sup.8).dbd.C(R.sup.9)--;
- n is 0, 1 or 2;
- m is 2, 3 or 4;
- s is 1 or 2;
- Y is --O--, --S(O).sub.n -- and --N(R.sup.12)--;
- R.sup.7 is:
- (a) H,
- (b) (C.sub.1 -C.sub.6)-alkyl,
- (c) phenyl,
- (d) (C.sub.1 -C.sub.6)-alkylphenyl, or
- (e) (C.sub.3 -C.sub.7)-cycloalkyl;
- R.sup.8 and R.sup.9 are independently:
- (a) H,
- (b) (C.sub.1 -C.sub.6)-alkyl or (C.sub.2 -C.sub.6)-alkenyl each of which is unsubstituted or substituted with one or two substituents selected from the group consisting of:
- i) --OH,
- ii) --O--(C.sub.1 -C.sub.4)-alkyl,
- iii) --S(O).sub.n --(C.sub.1 -C.sub.4)-alkyl,
- iv) --NR.sup.7 --(C.sub.1 -C.sub.4)-alkyl,
- v) --NHR.sup.7,
- vi) --COOR.sup.7,
- vii) --CONHR.sup.7,
- viii) --OCOR.sup.12, or
- ix) --CONR.sup.7 R.sup.12,
- (c) (C.sub.3 -C.sub.7)-cycloalkyl,
- (d) F, Cl, Br, I,
- (e) CF.sub.3,
- (f) --COOR.sup.7,
- (g) --CONR.sup.7 R.sup.12,
- (h) --NR.sup.7 R.sup.12,
- (i) --NR.sup.7 CONR.sup.7 R.sup.12,
- (j) --NR.sup.7 COOR.sup.12,
- (k) --SO.sub.2 NR.sup.7 R.sup.12,
- (l) --O--(C.sub.1 -C.sub.4)-alkyl,
- (m) --S(O).sub.n --(C.sub.1 -C.sub.4)-alkyl, or
- (n) --NHSO.sub.2 R.sup.12 ;
- R.sup.10 is:
- (a) H,
- (b) (C.sub.1 -C.sub.4)-alkyl unsubstituted or substituted with one of the following substituents:
- i) --OH,
- ii) --NR.sup.7 R.sup.12,
- iii) --COOR.sup.7,
- iv) --CONHR.sup.7, or
- v) --CONR.sup.7 R.sup.12, or
- (c) Cl, or F;
- R.sup.12 is
- (a) (C.sub.1 -C.sub.6)-alkyl, unsubstituted or substituted with a substituent selected from the group consisting of:
- i) --OR.sup.7,
- ii) --NR.sup.7 !.sub.2,
- iii) --NH.sub.2,
- iv) --COOR.sup.7,
- v) --NCH.sub.2 CH.sub.2 !.sub.2 Q,
- vi) --CF.sub.3, or
- vii) --CON(R.sup.7).sub.2 ;
- (b) aryl, wherein aryl is defined as phenyl or naphthyl which is unsubstituted or substituted with one or two substituents selected from the group consisting of:
- i) (C.sub.1 -C.sub.4)-alkyl,
- ii) --O--(C.sub.1 -C.sub.4)-alkyl,
- iii) --CONR.sup.7 !.sub.2,
- iv) F, Cl, Br or I,
- v) --COOR.sup.7,
- vi) --NH.sub.2,
- vii) --NH(C.sub.1 -C.sub.4)-alkyl!,
- viii) --N(C.sub.1 -C.sub.4)-alkyl!.sub.2, or
- ix) --CONCH.sub.2 CH.sub.2 !.sub.2 Q;
- (c) --(C.sub.1 -C.sub.4)-alkylaryl, wherein aryl is as defined above,
- (d) (C.sub.3 -C.sub.7)-cycloalkyl,
- (e) ##STR45## or (f) CF.sub.3 ;
- R.sup.7 and R.sup.12 on the same nitrogen atom they may join together to form a ring selected from the group consisting of:
- morpholinyl, piperazinyl, or pyrrolyl, or
- Q is O, S or --NR.sup.7 ;
- which comprises alkylating a derivative ##STR46## wherein X is Cl, Br, I, Omesylate, Otosylate or Otriflate;
- with an aryloxy derivative:
- ##STR47## wherein M.sup.+ is Na.sup.+, K.sup.+, Li.sup.+, or N(R.sup.16).sub.4.sup.+ ;
- and R.sup.16 is H or (C.sub.1 -C.sub.6)-alkyl;
- in an organic solvent at a temperature range of about -60.degree. C. to about 30.degree. C. for about 30 minutes to 30 hours to give an alkylated derivative bearing the chiral auxiliary:
- ##STR48##
106 more elements
Dependencies are inferred from the claim text.