Patent ID: 8063251

Claim:
A process for the preparation of optically pure R (−) salbutamol of the formula (6): and its pharmaceutically acceptable salts, the process comprising: a) dissolving a racemic mixture of 4-benzyl salbutamol of the formula (1): and (+) 4-nitro tartranilic acid of the Formula (2): in a binary solvent system comprising alkyl acetate and alcohol at refluxed temperature to form a solution; b) cooling the solution to crystallize out 4-nitro tartranilic acid salt of (R)-isomer of 4-benzyl salbutamol of the formula (3): and isolating the compound of formula (3) by filtration to leave 4-nitro tartranilic acid salt of (S)-isomer of 4-benzyl salbutamol of the formula (7): and traces of the compound of the formula (3) in the filtrate; c) purifying the 4-nitro tartranilic acid salt of (R)-isomer of 4-benzyl salbutamol of the formula (3) by treating it with a binary solvent system comprising alkyl acetate and alcohol and isolating the compound of the formula (3) by filtration; d) treating 4-nitro tartranilic acid salt of (R)-isomer of 4-benzyl salbutamol of the formula (3) with 5 to 15 percent formic acid solution to obtain formic acid salt of (R)-isomer of 4-benzyl salbutamol of the formula (4): and liberate (+) 4-nitro tartranilic acid of the formula (2); e) separating out the (+) 4-nitro tartranilic acid of the formula (2) by filtration; f) cooling the filtrate containing formic acid salt of (R)-isomer of 4-benzyl salbutamol of the formula (4) to 5 to 10 degree Celsius followed by basifying the filtrate to pH 9 to 9.5 by adding a base to obtain enantiomeric pure (R)-isomer of 4-benzyl salbutamol of the formula (5): and isolating the (R)-isomer by extracting it with methylene chloride followed by distilling out the solvent to obtain a residue, treating the residue with toluene at 80 to 85 degree Celsius, cooling the solution to 0 to 5 degree Celsius to precipitate optically pure (R)-isomer and filtering the optically pure (R)-isomer of formula (5); and g) debenzylating the (R)-isomer of the formula (5) to obtain optically pure (R) isomer of Salbutamol of the formula (6):