(E)-(4R)-4,5-Isopropylidene-dioxy-1-(2-hydroxy-5-fluorophenyl)propenone synthesis

Yield:-

Reaction Conditions:

in water at 20;

Steps:

9 Example 9; (E)-(4S)-4,5-isopropylydene-dioxy-1-(2-hydroxy-5-fluoro-phenyl)-prop-2E-ene-1-one (IX-S compound)

The pH to 5,5 of the suspension 85,5 g (0,4 moles) of sodium periodate in 200 ml of water is adjusted with dropping a solution about 16 g (0,4moles) of sodium hydroxide in 130 ml of water into the reaction mixture between 0-7°C. 43,6 g (0,2 moles) of 5,6- isopropylydene-L-gylono-1, 4-lactone is added to the given oxidizer mixture under 30°C, the pH is kept at 5,5 with adding a 15% aqueous, solution of sodium hydrogen carbonate until reaction is finished. The reaction mixture is stirred for additional 30 minutes. Then the pH is adjusted to 6,7 with adding a 15% aqueous ; solution of sodium hydrogen carbonate. 100 g of sodium chloride is added to the given suspension, filtered, the compound on the filter is washed 3X100 ml dichloromethane. Filtrates are collected, dried over sodium sulphate, then filtered. The obtained solution containing L (-) S-O, O-ISOPROPYLYDENE- glycerinealdehyde (VIII-S) is stirred and 66g (0,16 moles) of 1- (5- FLUORO-2-HYDROXY-PHENYL)-2- (TRIPHENYL-X5-PHOSPHANILYDENE)-ETHANONE is added, and stirred overnight at room temperature. Then the solution is extracted with 2x50 ml of water, dried over magnesium sulphate, the solvent is evaporated in vacuum. 200 ml of diethyl ether is added to the given oily product then stirred for 10 minutes at room temperature. The precipitated crystalline triphenylphosphin oxide is filtered, and washed with 3X50 ml of diethyl ether. The filtrate is evaporated in vacuum, the residue is about 100 g. Then 50 ml of isopropanol is added to the residue at room temperature under stirring. The reaction mixture is stirred for additional 10 minutes, then filtered, the crystalline is washed with 2x 10 ML of isopropanol. Thus 22,4g (42, 1%) titled product is obtained. Mp.: 79-81OC. The filtrate is evaporated to 100 ml, is left to stay overnight in fridge, then the precipitated crystalline is filtered, washed with 2X10 ml cold (5°C) isopropanol. Thus 10,4 g (19,5%) second product is obtained. Mp.: 80- 82°C. Both products are ready to use in the subsequent reaction. The total yield is 61,6% the optical rotation of product is [?]D20(C=1, CHCL3)=-28,1°.

References:

WO2004/41805,2004,A1 Location in patent:Page 46-48