SI8910630B - Process for obtaining novel alkanophenones - Google Patents

Claims (18)

1 l. A process for the preparation of compounds of formula I, in which R 1 represents lower alkyl or mono-, di- or polyfluoroalkyl, R 2 represents hydrogen, lower alkyl, lower alkenyl or mono-, di- or polyfluoroalkyl alkyl, X represents C 1 -C 3 -alkylphene, oxy or thio, alk represents lower alkylene, n stands for 1 or 2, R3 stands for unsubstituted or lower alkyl, lower alkoxy, halogen, carboxy, lower alkoxycarbonyl, amino N-mono- or Ν, d-di-alkylamino, carbamoyl, N-mono- or Ν, Ν - lower phenyl substituted alkylcarbamoyl and / or trifluoromethyl; or stands for lower alkyl, mono-, di- or trifluoroalkyl alkyl, carboxy-lower alkyl, lower alkoxy carbonyl lower alkyl, carbamoyl-lower alkyl or N-mono- or Ν, Ν-lower alkylcarbamoyl-lower alkyl, R4 represents carbonyl , 5-tetrazolyl, carbamoyl, N-mono- or N, N-di-alkylcarbamoyl or unsubstituted or substituted in the phenyl part by lower alkyl, lower alkoxy, halogen and / or trifluoromethyl substituted N- (benzenesulfonyl) carbamoyl and stands for R5 for hydrogen or lower alk ; where they do not have a " lower " Designated residues of more than 7 carbon atoms; and their salts, characterized in that the epoxide of formula II z in which R 1, R 2, X, alk, n m R 3 are as defined in formula I, are reacted with a thiol of formula III, (III) wherein R * and R5, as defined in formula I, or a salt thereof, and optionally a compound which can be obtained, according to the process, are converted into another compound of formula I, a mixture of stereoisomers which can be obtained in the sense of a process, is separated into components and / or a free compound which can be obtained in the sense of the process, converted into a salt or a salt which can be obtained in the sense of the process, converted into a free compound or into another salt. A process according to claim 1 for the preparation of compounds of formula I, in which R 1 represents C 1 -C 4 alkyl, or Q 1, a, trifluoro-C 1 -C 4 -alkyl, R 2 represents hydrogen, C 1 -C 4 -alkyl, C2-C4-alkenyl or m, m, m-trifluoro-C1-C4-alkyl, X represents C1-C3-alkylene, oxy or thio, alk represents the level of C2-C6-alkylene, n stands for 1 or 2, R3 stands for unsubstituted or with C1-C4-alkyl, C1-C4-alkoxy, halogen with an atomic number up to and including 35, trifluoromethyl, carboxy and / or C1-C4-alkoxycarbonyl substituted phenyl, or for C1-C7-alkyl, m, m, m- trifluoro-C2-C5-alkyl, carboxy-C2-C5-alkyl or C1-C4alkoxycarbonyl-C2-C8-alkyl, R4 represents carboxy or N- (benzenesulfonyl) carbamoyl and stands for R5 for hydrogen, and their salts. Process according to one of Claims 1 to 2 for the preparation of compounds of the formula I in which R 1 represents C 1 -C 4 -alkyl or m, ro, α-trifluoro-C 1 -C 4 -alkyl, R 2 represents C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl or m, m, m-trifluoro-C1-C4-alkyl, and the group X is attached in the position of the pair with respect to the group Rt C (= O) -, and their salts. A process according to claim 1 for the preparation of compounds of formula Ia 3 wherein R 1 represents C 1 -C 4 -alkyl, R 2 represents C 1 -C 4 -alkyl, C 2 -C 4 -alkenyl or ω, ω, ω-trifluoro-C 1 -C 4 -alkyl, X represents C 1 -C 3 -alkylene, oxy or thio, alk represents level C2-C6-alkylene, n represents 1 or 2, R3 represents a group of formula -A-R3 'in which -A- represents C1-C4-alkylene, phenylene or a direct bond and R3' represents C1-C4- alkyl, trifluoromethyl, carboxy or C1-C4-alkoxycarbonyl, R4 represents carboxy or N- (benzenesulfonyl) carbamoyl and stands for R5 for hydrogen, and their salts. A process according to claim 4 for the preparation of compounds of formula Ia, in which R 1 represents C 1 -C 4 -alkyl, R 2 represents C 1 -C 4 -alkyl, X represents oxy, alk represents C 2 -C 6 -alkylene, n represents 1 or 2, R 3 represents C 1 -C 4 -alkyl, C 1 -C 4 -alkoxy, halogen with an atomic number up to and including 35, trifluoromethyl or C 1 -C 4 -alkoxycarbonyl substituted phenyl; or for C2-C8-alkyl, m, m, m-trifluoro-C3-C5-alkyl or C1-C4-alkoxycarbonyl-C1-C4-alkyl, R4 represents carboxy and R5 is hydrogen, and their salts. A process according to claim 4 for the preparation of compounds of formula Ia, in which R 1 represents C 1 -C 4 -alkyl, R 2 represents C 1 -C 4 -alkyl, X represents oxy, alk represents C 2 -C 6 -alkylene, n represents 2, R3 represents a group of formula -A-R3 in which -A- represents C1-C4-alkylene or k-phenylene and Ro 'represents C1-C4-alkyl, trifluoromethyl or C1-C4-alkoxycarbonyl, R4 represents carboxy or N- (benzenesulfonyl) -carbamoyl and R5 is hydrogen, m of their salts. Process according to one of Claims 1 to 4 for the preparation of compounds of formula I or in which X represents oxy, m of their salts Process according to one of Claims 1 to 5 for the preparation of compounds of formula I or la, in which n stands for 2, m of their salts. Process according to one of Claims I to 8 for the preparation of compounds of formula I or Ia in which R3 represents m-C1-C4-alkylphenyl or m-trifluoromethylphenyl, R, carboxy and R5 hydrogen, and their salts Process according to one of Claims 1 to 9 for the preparation of compounds of formula I or 1a, in which the nearest double bond of the residue - (CH = CH) n- in (Z) -, i. cis-configuration, and optionally an additional double bond of the residue - (CH = CH) n- in (E) -, i.e. trans-configuration, and their salts. Process according to one of Claims 1 to 10 for the preparation of compounds of formula I or Ia, in which the chain atom C attached to the sulfur atom has the (S) -configuration and the chain atom C bearing the hydroxy group, the (R) -configuration, and their salts. Process according to Claim 1 for the preparation of (1R, 2S) -1-hydroxy-1- (3-trifluoromethylphenyl) -8- (4-acetyl-3-hydroxy-2-propyl “phenoxy) -octa-3 (E) , 5 (Z) -dien-2-yl-7-thio-4-oxo-4H-1-benzopyran-2-carboxylic acid or its sodium salt. Process according to Claim 1 for the preparation of (1R, 2S) -1-hydroxy-1- (3-methylphenyl) -8- (4-acetyl-3-hydroxy-2-propylphenoxy) -octa-3 (E), 5 (Z) -Dien-2-yl-7-thio-4-oxo-4H-1-benzopyran-2-carboxylic acid or its sodium salt. ε Process according to Claim 1 for the preparation of (4R, 5S) -1,1,1-trifluoro-4-hydroxy-11- (4-acetyl 3-hydroxy-2-propylphenoxy) -undeca-6 (E), (Z) -Dien-5-yl-7-thio-4-oxo-4H-1-benzopyran-2-carboxylic acid or its sodium salt Process according to Claim 1 for the preparation of (1R, 2S) -1-hydroxy-1- (3-trifluoromethylphenyl) -9 (4-acetyl-3-hydroxy-2-propyl-phenoxy) -nona-3 (E), 5 (Z) -Dien-2-yl-7-thio-4-oxo-4H-1-benzopyran-2-carboxylic acid or its sodium salt. A process according to claim 1 for the preparation of (IR, 2S) -1-hydroxy-1- (3-trifluoromethylphenyl) -11 (4-acetyl-3-hydroxy-2-propyl-phenoxy) -undeca-3 (E), 5 (Z) -Dien-2-yl-7-thio-4-oxo-4H-1-benzopyran-2-carboxylic acid or its sodium salt. Process according to Claim 1 for the preparation of (1R, 2S) -1-hydroxy-1- (3-chlorophenyl) -10- (4-acetyl-3-hydroxy-2-propylphenoxy) -deca-3 (E), 5 Z) -dien-2-yl-7-thio-4-oxo-4H-1-benzopyran-2-carboxylic acid or its sodium salt. A process according to claim 1 for the preparation of (1R, 2S) -1-hydroxy-1- (3-methoxyphenyl) -10- (4-acetyl-3-hydroxy-2-propyl-phenoxy) -deca-3 (E), 5 (Z) -Dien-2-yl-7-thio-4-oxo-4H-1-benzopyran-2-carboxylic acid or its sodium salt