Process for the preparation of tapentadol and analogs thereof

A process for the preparation of tapentadol and analogs or stereoisomers or compounds of formula (I);

• wherein, A is aryl, heteroaryl, and cycloalkyl;
• R is H, OH, OR1, halogen, C1-C12 alkyl, cycloalkyl, aryl or heteroaryl;
• R1 is C1-C12 alkyl, cycloalkyl, aryl or heteroaryl, wherein each of these groups may further be substituted with one or more substituent selected from H, OH, halogen, CN, NO2, C1-C4 alkyl or phenyl;
• comprising the steps of:
• i) treating tetrahydro-4H-thiopyranone (V) with 40% aqueous solution of dimethylamine and 36% aqueous solution of formaldehyde, to obtain compound of formula (IV),
• ii) reacting compound of formula (IV) as obtained from step i) with magnesium turnings and
• to obtain compound of formula (III);
• wherein, A is aryl, heteroaryl, and cycloalkyl;
• R is H, OH, OR1, halogen, C1-C12 alkyl, cycloalkyl, aryl or heteroaryl;
• R1 is C1-C12 alkyl, cycloalkyl, aryl or heteroaryl, wherein each of these groups may further be substituted with one or more substituent selected from H, OH, halogen, CN, NO2, C1-C4 alkyl or phenyl;
• and
• X is halide;
• iii) treating compound of formula (III) as obtained from step ii) with acid followed by a reducing agent in presence of an organic solvent to undergo an dehydroxylation and/or elimination reaction to obtain crude compound of formula (II) as a mixture of compounds of formula (IIa) and (IIb);
• and
• iv) reducing the crude compound of formula (II) as obtained from step iii) with transition metal containing reducing agent in presence of an alcoholic solvent to undergo sulphur removal, to obtain compound of formula (I);
• v) optionally, hydrolysing compound of formula (I), wherein R═OR1 is converted to R═OH, by reacting compound of formula (I) with a mineral acid
• wherein the steps (i) to (iv) are purification free steps.