11  US 7,638,642 B2  12  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.  (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.  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  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)  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)  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.  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)  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.  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  OCOBiPh  THF/MeOH  H20  K2C03  OCOBiPh  _)---0----0  4-BiPhCOCl  TEA 