Patent GB-1002851-A (GB)
Title: 1-methyl-3-(m-hydroxyphenyl)-3-alkylpyrrolidines and ethers and esters thereof and their acid addition salts
Inventor: CAVALLA JOHN FREDERICK
Filed: 1961-01-04
Abstract: The invention comprises racemic and optically active compounds of the general formula <FORM:1002851/C2/1> (wherein R represents a hydrogen atom or a lower alkyl or lower alkanoyl radical, R1 represents a C2- 4 alkyl radical, and R2 and R3 each represents a hydrogen atom or a methyl or ethyl radical, R2 and R3 being chosen such that they are not both alkyl radicals) and pharmaceutically acceptable acid-addition salts thereof, pharmaceutical preparations containing them, and their preparation by (a)-when R is a hydrogen atom or a lower alkyl radical and R2 and R3 are both hydrogen atoms-reducing a compound of the formula <FORM:1002851/C2/2> with a complex metal hydride (when R in the starting material is an alkonoyl radical, R in the product is a hydrogen atom), (b)-when R is a hydrogen atom-heating a corresponding 1-methyl - 3 - (m - alkoxyphenyl) - 3 - alkyl-pyrrolidine with an acidic reagent capable of cleaving the ether linkage, (c)-when R is a lower alkanoyl radical-acylating the corresponding phenol, (d) methylating a compound of the formula <FORM:1002851/C2/3> or (e)-when R is a lower alkyl radical, R2 is a methyl or ethyl radical and R3 is a hydrogen atom-reducing a compound of the formula <FORM:1002851/C2/4> (wherein R4 represents a methyl or ethyl radical and A(-) represents an anion), optionally followed in each case by acid addition salt formation. An optically active product may be obtained by using an optically active starting material or by resolving a racemic product. The terms "lower alkyl radical" and "lower alkanoyl radical" are defined as radicals containing not more than four carbon atoms.  The following intermediates are prepared from the starting materials indicated in parentheses: N - methyl - a  - (m - methoxyphenyl) - a  - propylsuccinimide (ethyl - a  - cyano - b  - (m - methoxyphenyl) - b - propylacrylate, via ethyl a ,b  - dicyano - b  - (m - methoxyphenyl) - hexanoate and a  - (m - methoxyphenyl) - a  - propylsuccinic acid); 5 - methyl - 3 - (m - methoxyphenyl) - 3 - propylpyrrolidin (a  - (m - methoxyphenyl) - valeronitrile, via 4-cyano-4-(m - methoxyphenyl) - heptanol - 2 and 4 - aminomethyl - 4 - (m - methoxyphenyl) - heptanol - 2); 3 - (m - methoxyphenyl) - 3 - propylpyrrolidine (a  - (m - methoxyphenyl) - a  - propylsuccinic acid, via N - benzyl - a  - (m - methoxyphenyl) - a  - propylsuccinimide and 1 - benzyl - 3 - (m - methoxyphenyl) - 3 - propylpyrrolidine, or 2 - (21 - chloroethyl) - 2 - (m - methoxyphenyl) - valeronitrile); 1,2 - dimethyl - 3 - (m - methoxyphenyl - 3 - propyl - 1 - pyrrolinium iodide (m-methoxybenzyl cyanide, via a  - (m - methoxyphenyl) - valeronitrile, 3 - cyano - 3 - (m - methoxyphenyl) - 1 - chlorohexane and 2 - methyl - 3 - (m - methoxyphenyl) - 3 - propyl - 1 - pyrroline.  The compounds of the invention are analgesics and may be administered orally or parenterally in the form of pharmaceutical preparations containing them in association with a carrier or diluent.  Reference has been directed by the Comptroller to Specification 928,007.