content_image/944615.jpg content_image/944614.jpg content_image/944616.jpg content_image/944613.jpg
(TLC), 36 g of anhydrous magnesiumsulfate was added to the reaction mixture, and stirred for 20 min. The resulting mix› ture was filtered and distilled under a reduced pressure at 30° C. to remove the solvent, and the residue was further sub› jected in distillation under an atmospheric pressure at 55° C. 5 to completely remove the solvent. The reacting residue was distilled at 10 torr, about 40° C. to obtain 61.6 g (yield 86%) of the title compound as a colorless liquid. 

NMR (300 MHz, CDC1$_{3}$ ): 1.41(s, 3H), 1.47(s, 3H), 10 4.07-4.19(m, 2H), 4.35-4.40(m, lH), 9.71(s, lH) 

Step 3: Preparation of ethyl 2,2-difluoro-3-hydroxy-3-(2,2- dimethy 1-[ 1,3 ]dioxoran-4-yl )propionate 

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13 g of zinc was added to 26 ml oftetrahydrofuran, 0.51 ml of dibromoethane was added thereto, and the mixture was kept at 60° C. for 1 min. 0.76 ml of chlorotrimethylsilane was added thereto at 40° C., and the mixture was allowed to react for 10 min. The reaction mixture was heated to 60° C., a solution made of 25.5 ml of ethyl bromodifluoroacetate, 30.8 g of the compound obtained in step 2 and 39 ml oftetrohy› drofuran was added dropwise thereto, and the mixture was refluxed for 30 min. After adding 65 ml of diethyl ether and 260 g of ice thereto, 260 ml of 1 N HCl was added thereto and stirred until the ice was completely melted. The aqueous layer was extracted three times with 90 ml portion of diethyl ether, the combined organic layer was washed successively with 65 ml portion of NaCl and sodium bicarbonate, dried over anhy- drous magnesiumsulfate, and filtered .. After removing the solvent, the residue was distilled at 10 torr to obtain 28.9 g (57%) of the title compound (R:S=3:1) at 130-134° C. as a colorless liquid. 

NMR (300 MHz, CDC1$_{3}$ ): 1.31-1.52(m, 9H), 2.67(s, lH, (R)-OH), 2.90(d, lH, (S)-OH), 3.7-4.4(m, 6H) 

In the following Examples, the term "-OCOBiPh" or "BiPhOCO-" refers to 

HPLC analyses of the compounds of formulas (I) and (III) were performed with a YMC pack pro Cl 8 RS ( 4.6xl 50 mm, 5 µm) colunm using a mixture of a buffer and acetonitrile (65:35, v/v) (for the compound of formula (III)) or 80% acetonitrile (for the compound of formula (I)) as an eluent. 

<img src='content_image/944614.jpg'>

The buffer was prepared by mixing 7 .0 g ofN a Cl O 4 , 1. 7 4 g of K$_{2}$BPO $_{4 }$and 1 L of water, and adding H$_{3}$PO $_{4 }$thereto until pH 2.75. 

Preparation of ethyl 2,2-difluoro-3-( 4-biphenylcar› bonyl)oxy-3-(2,2-dimethyl-[1,3]dioxoran-4-yl)propi› onate (the compound of formula (IV); R=4-bicarbo› nyl) 

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50.0 g of the compound obtained in Preparation 1 was added to 500 ml of methylene chloride, 42 ml oftriethylamine and 51.1 g of 4-biphenylcarbonyl chloride were added thereto, and the mixture was kept at room temperature for 6 hours. After adding 360 ml of 1 N HCl thereto, the organic layer was successively washed with 180 ml portion of water, saturated sodium bicarbonate and NaCl, and dried over mag› nesiumsulfate. The residue was filtered, and distilled under a reduced pressure to obtain 83.7 g (yield 98%) of the title compound as a cream-color liquid. 

NMR (300 MHz, CDC1$_{3}$ ): 1.25-1.74(m, 9H), 4.11-4.19 (m, 2H), 4.30-4.36(m, 2H), 4.56-4.58(m, 2H), 5.72-5.83 (ddd, 1Hx1/2), 5.88-6.02(ddd, 1Hx 2 /2), 7.42-7.53(m, 3H), 7.63-7.73(dd, 4H), 8.15-8.17(d, 2H) 

Preparation of potassium 2,2-difluoro-3R-( 4-biphe› nylcarbonyl)oxy-3-(2,2-dimethyl-[1,3]dioxoran-4-yl) propionate (the compound of formula (III); R=4- biphenylcarbonyl) 

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MethodA 

83.8 g of the compound obtained in Example 1 was added to 1.4 L of a mixture of tetrahydrofuran and methanol (2:3, 

## EXAMPLE 1 

## EXAMPLE2 

