Patent ID: 6376683
Filing Date: 2002-04-23
Classification: C07D,Y02P

Abstract:
An improved process for the synthesis of (4R,6S)-4-hydroxy-6-hydroxymethyl tetrahydro-pyran-2-one which comprisesi) reacting the (s)-(âˆ’)-Malic acid with a mixture of mineral acid and alcohol at room temperature for a period of 18 to 30 hrs to obtain the diester of (S)-(âˆ’) Malic acid of formula (4) ii) reducing the compound (4) with a hydride reducing reagent at room temperature to reflux temperature for a period of 8 to 12 hrs to obtain (S)-1,2,4-butanetriol of formula (5) iii) treating the compound (5) with protecting reagent at room temperature for a period of 36 to 48 hrs to obtain (S)-1,2,4-butanetriol 1,2-acetonide of formula (6) iv) oxidizing compound (6) using oxidizing reagents at âˆ’78Â° C. for a period of 1 to 2 hrs to obtain the aldehyde in situ, treating the aldehyde with a phosphorous ylide at room temperature for a period of 18 to 24 hrs to obtain (5S)-trans-5,6-dihydroxy-2-hexenoate 5,6-acetonide of formula (7) v) treating compound (7) with osmium tetraoxide and a chiral ligand at 0Â° C. for a period of 12 to 24 hrs to obtain (2S,3R,5S)-ethyl-trans-2,3,5,6-tetrahydroxy-hexanoate 5,6-acetonide of formula (8) vi) treating compound (8) with a halide of sulphuryl or thionyl reagent at 0Â° C. for a period of 30 to 40 mins to obtain (4R)-carbethoxy-(5S)-di-O-isopropylidine propyl-1,3,2-oxathiolane-2-oxide of formula (9) vii) reacting the compound (9) with a hydride based reagent at room temperature in inert atmosphere for a period of 8 to 12 hrs, hydrolyzing the reaction mixture with a mineral acid to obtain the product of formula (1)