Process for the preparation of propionic acid derivatives

Abstract

or a salt thereof.

1 . A process for the preparation of a compound of formula (I) 
       
         
           
           
               
               
           
         
       
       or a salt thereof, wherein a compound of formula (II) 
       
         
           
           
               
               
           
         
       
       or a salt thereof is hydrogenated
 (e) in the presence of a catalyst comprising iridium; or 
 (f) in the presence of a catalyst comprising ruthenium; and
 a compound of: formula (III), 
 
 
       
         
           
           
               
               
           
         
         
           formula (IV), 
         
       
       
         
           
           
               
               
           
         
         
           formula (V), 
         
       
       
         
           
           
               
               
           
         
         
           formula (VI), 
         
       
       
         
           
           
               
               
           
         
         
           or formula (VII), 
         
       
       
         
           
           
               
               
           
         
       
       wherein
 R 3  is alkyl, cycloalkyl or aryl; 
 R 4  is cycloalkyl, aryl or heteroaryl; 
 R 5  is cycloalkyl or aryl; 
 R 6  is cycloalkyl or aryl; 
 R 7  is cycloalkyl or aryl; 
 R 8  is cycloalkyl or aryl; and 
 R 9  is cycloalkyl or aryl. 
 
     
     
         2 . A process according to  claim 1 , wherein the catalyst comprises iridium and a compound of formula (III), 
       
         
           
           
               
               
           
         
       
       formula (VIII), 
       
         
           
           
               
               
           
         
       
       or formula (IX), 
       
         
           
           
               
               
           
         
       
       wherein
 R 1  is selected from the group consisting of: hydrogen, alkyl, aryl and arylalkyl; 
 R 2  is aryl; and 
 R 10  is aryl. 
 
     
     
         3 . A process according to  claim 2 , wherein the catalyst comprises iridium and a compound of formula (III) 
       
         
           
           
               
               
           
         
       
     
     
         4 . A process according to  claim 1 , wherein the catalyst comprises iridium and a compound of formula (X) 
       
         
           
           
               
               
           
         
       
       wherein:
 R 1  is selected from the group consisting of: hydrogen, alkyl, aryl and arylalkyl; and 
 R 2  is aryl. 
 
     
     
         5 . A process according to  claim 2 , wherein R 1  is selected from the group consisting of: hydrogen, iso-propyl, phenyl and benzyl. 
     
     
         6 . A process according to  claim 2 , wherein R 2  is selected from the group consisting of: phenyl, 3,5-di-methylphenyl and 3,5-di-tert-butyl-phenyl. 
     
     
         7 . A process according to  claim 2 , wherein R 10  is 3,5-di-methyl-phenyl. 
     
     
         8 . A process according to  claim 2 , wherein the compound of formula (III) is selected from the group consisting of:
 (S a ,S)-7-[4,5-Dihydro-4-benzyloxazol-2-yl]-7′-diphenylphosphino-1,1′-spirobiindane;   (S a ,S)-7-[4,5-Dihydro-4-benzyloxazol-2-yl]-7′-di(3,5-di-methylphenyl)phosphino-1,1′-spirobiindane;   (S a ,S)-7-[4,5-Dihydro-4-benzyloxazol-2-yl]-7′-di(3,5-di-tert-butylphenyl) phosphino-1,1′-spirobiindane;   (S a ,S)-7-[4,5-Dihydro-4-phenyloxazol-2-yl]-7′-di(3,5-di-tert-butylphenyl) phosphino-1,1′-spirobiindane;   (S a ,S)-7-[4,5-Dihydro-4-isopropyloxazol-2-yl]-7′-di(3,5-di-tert-butylphenyl) phosphino-1,1′-spirobiindane; and   (S a )-7-[4,5-Dihydrooxazol-2-yl]-7′-di(3,5-di-tert-butylphenyl)phosphino-1,1′-spirobiindane.   
     
     
         9 . A process according to  claim 2 , wherein the compound of formula (III) is selected from the group consisting of:
 (S a ,S)-7-[4,5-Dihydro-4-benzyloxazol-2-yl]-7′-di(3,5-di-tert-butylphenyl) phosphino-1,1′-spirobiindane;   (S a ,S)-7-[4,5-Dihydro-4-isopropyloxazol-2-yl]-7′-di(3,5-di-tert-butylphenyl) phosphino-1,1′-spirobiindane; and   (S a )-7-[4,5-Dihydrooxazol-2-yl]-7′-di(3,5-di-tert-butylphenyl)phosphino-1,1′-spirobiindane.   
     
     
         10 . A process according to  claim 4 , wherein the compound of formula (X) is selected from the group consisting of:
 (S a ,R)-7-[4,5-Dihydro-4-benzyloxazol-2-yl]-7′-diphenylphosphino-1,1′-spirobiindane;   (S a ,R)-7-[4,5-Dihydro-4-benzyloxazol-2-yl]-7′-di(3,5-di-methylphenyl)phosphino-1,1′-spirobiindane;   (S a ,R)-7-[4,5-Dihydro-4-benzyloxazol-2-yl]-7′-di(3,5-di-tert-butylphenyl) phosphino-1,1′-spirobiindane;   (S a ,R)-7-[4,5-Dihydro-4-phenyloxazol-2-yl]-7′-di(3,5-di-tert-butylphenyl) phosphino-1,1′-spirobiindane; and   (S a ,R)-7-[4,5-Dihydro-4-isopropyloxazol-2-yl]-7′-di(3,5-di-tert-butylphenyl) phosphino-1,1′-spirobiindane.   
     
     
         11 . A process according to  claim 2 , wherein the catalyst is Ir(L 1 )(L 2 ) n Y wherein:
 Ir is iridium;   L 1  is a compound of formula (III), (VIII) or (IX);   L 2  is selected from the group consisting of: cyclooctene, 1,5-cyclooctadiene, ethylene, 1,5-hexadiene and norbornadiene;   Y is selected from the group consisting of: chloride, iodide, bromide, fluoride, trifluoroacetate, tetrafluoroborate, tetrakis[3,5-bis(trifluoromethyl)phenyl]borate, tetraphenylborate, hexafluoroantimonate, hexafluorophosphate, triflate, mesylate, perchlorate, perbromate, periodate, nitrate, hydrogen sulfate and acetylacetonate; and   n is 1 or 2.   
     
     
         12 . A process according to  claim 4  wherein the catalyst is Ir(L 1 )(L 2 ) n Y wherein:
 Ir is iridium; 
 L 1  is a compound of formula (X); 
 L 2  is selected from the group consisting of: cyclooctene, 1,5-cyclooctadiene, ethylene, 1,5-hexadiene and norbornadiene; 
 Y is selected from the group consisting of: chloride, iodide, bromide, fluoride, trifluoroacetate, tetrafluoroborate, tetrakis[3,5-bis(trifluoromethyl)phenyl]borate, tetraphenylborate, hexafluoroantimonate, hexafluorophosphate, triflate, mesylate, perchlorate, perbromate, periodate, nitrate, hydrogen sulfate and acetylacetonate; and 
 n is 1 or 2. 
 
     
     
         13 . A process according to  claim 1 , wherein the catalyst is selected from the group consisting of:
 [Ir((S,S)-7-[4,5-dihydro-4-benzyloxazol-2-yl]-7′-di(3,5-di-tert-butylphenyl) phosphino-1,1′-spirobiindane)(1,5-cyclooctadiene)][tetrakis[3,5-bis(trifluoromethyl)phenyl]borate];   [Ir((S,S)-7-[4,5-dihydro-4-benzyloxazol-2-yl]-7′-di(3,5-di-tert-butylphenyl) phosphino-1,1′-spirobiindane)(1,5-cyclooctadiene)][tetrafluoroborate];   [Ir((S,S)-7-[4,5-dihydro-4-benzyloxazol-2-yl]-7′-di(3,5-di-tert-butylphenyl) phosphino-1,1′-spirobiindane)(1,5-cyclooctadiene)][trifluoromethanesulfonate];   [Ir((S,S)-7-[4,5-dihydro-4-benzyloxazol-2-yl]-7′-di(3,5-di-tert-butylphenyl) phosphino-1,1′-spirobiindane)(1,5-cyclooctadiene)][chloride];   [Ir((S,S)-7-[4,5-dihydro-4-isopropyloxazol-2-yl]-7′-di(3,5-di-tert-butylphenyl) phosphino-1,1′-spirobiindane)(1,5-cyclooctadiene)][tetrakis[3,5-bis(trifluoromethyl)phenyl]borate]; and   [Ir((S)-7-[4,5-dihydrooxazol-2-yl]-7′-di(3,5-di-tert-butylphenyl)phosphino-1,1′-spirobiindane)(1,5-cyclooctadiene)][tetrakis[3,5-bis(trifluoromethyl) phenyl]borate].   
     
     
         14 . A process according to  claim 12 , wherein the catalyst is selected from the group consisting of:
 [Ir((S a ,R)-7-[4,5-dihydro-4-benzyloxazol-2-yl]-7′-di(3,5-di-tert-butylphenyl) phosphino-1,1′-spirobiindane)(1,5-cyclooctadiene)][tetrakis[3,5-bis(trifluoromethyl)phenyl]borate];   [Ir((S a ,R)-7-[4,5-dihydro-4-benzyloxazol-2-yl]-7′-di(3,5-di-tert-butylphenyl) phosphino-1,1′-spirobiindane)(1,5-cyclooctadiene)][tetrafluoroborate];   [Ir((S a ,R)-7-[4,5-dihydro-4-benzyloxazol-2-yl]-7′-di(3,5-di-tert-butylphenyl) phosphino-1,1′-spirobiindane)(1,5-cyclooctadiene)][trifluoromethanesulfonate]; and   [Ir((S a ,R)-7-[4,5-dihydro-4-benzyloxazol-2-yl]-7′-di(3,5-di-tert-butylphenyl) phosphino-1,1′-spirobiindane)(1,5-cyclooctadiene)][chloride].   
     
     
         15 . A process according to  claim 1 , wherein the catalyst comprises ruthenium and a compound of formula (IV), (V), (VI) or (VII). 
     
     
         16 . A process according to  claim 1 , wherein R 3  is selected from the group consisting of: tert-butyl, cyclohexyl, phenyl, 2-methyl-phenyl and 3,5-di-methyl-phenyl. 
     
     
         17 . A process according to  claim 1 , wherein R 4  is selected from the group consisting of: tert-butyl, cyclohexyl, phenyl, 3,5-di-trifluoromethyl-phenyl, 4-trifluoromethyl-phenyl, 3,5-di-methyl-4-methoxy-phenyl, 1-naphtyl and 2-furyl. 
     
     
         18 . A process according to  claim 1 , wherein R 5  is selected from the group consisting of: phenyl, cyclohexyl, 3,5-di-methyl-4-methoxy-phenyl and 3,5-di-methyl-phenyl. 
     
     
         19 . A process according to  claim 1 , wherein R 6  is selected from the group consisting of: phenyl, cyclohexyl, 3,5-di-methyl-phenyl, 3,5-di-trifluoromethyl-phenyl and norbornyl. 
     
     
         20 . A process according to  claim 1 , wherein R 7  is selected from the group consisting of: cyclohexyl, phenyl, 3,5-di-methyl-phenyl, 3,5-di-trifluoromethyl-phenyl, 3,5-di-methyl-4-methoxy-phenyl and 2-methyl-phenyl.