Potassium Carbonate → p-Toluenesulfonate

Participants

Reaction Conditions

Reaction Steps

(2R,4S)-2-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-ylmethyl)-4-tosyloxymethyl-1,3-dioxolane tosylate DTTT (23 tosylate salt) is prepared as follows: A suspension of (R)-tosyloxy-1,2-propanediol (10.0 g, 40 mmol) and 1-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-yl) ethanone (10.0 g, 39 mmol) in toluene (50 mL) is cooled to 5° C. Triflic acid (15 mL, 4 eq) is slowly added so that the temperature stays below 15° C. After complete addition the reaction mixture (2 phases) is stirred at 25° C. for 60 h. The mixture is diluted with ethyl acetate (EtOAc) (200 mL) and slowly dropped into a solution of K2CO3 (50 g) in water (400 mL) at 5° C. The organic layer is separated and the aqueous layer washed with EtOAc (150 mL). The combined organic extracts are dried over Na2SO4 (10 g) and filtered. A solution of toluenesulfonic acid (TsOH) (7.6 g monohydrate in EtOAc (50 mL) is slowly added at 25° C. The white solid product is filtered after 30 min, washed and dried to give cis DTTT containing 5% trans. Two crystallyzations from CH3CN (400 mL) gives 13.5 g pure (2R,4S)-DTTT (50% yield); [a]D25 =+16.6° (c=1, MeOH); ee=99.6%. The 2S,4R isomer is prepared in analogous fashion from (S)-tosyloxy-1,2-propanediol (14.8 g, 60 mmol) and 1-(2,4-dichlorophenyl)-2-(1H-1,2,4-triazol-1-yl) ethanone in (44% yield); [α]D25 =-16.6° (c=1, MeOH) ee=99.6%

Provenance & Evidence