(IO)  Patent No.:  US 7,638,642 B2  (45)  Date of Patent:  *Dec. 29, 2009  c12)  United States Patent  Lee et al.  (54)  METHOD FOR THE PREPARATION OF  D-ERYTHRO-2,2-DIFLUORO-2-DEOXY-1- OXORIBOSE DERIVATIVE  (75)  Inventors:  Jaeheon Lee,  Yongin-si (KR);  Gha-Seung Park,  Yongin-si (KR);  Moonsub Lee,  Daejeon (KR);  Cheol-Kyong Kim,  Suwon-si (KR);  Jae-Chui Lee,  Suwon-si (KR);  Young-Kil Chang,  Seoul (KR);  Gwan-Sun Lee,  Seoul (KR)  (73)  Assignee:  Hanmi Pharm, Co., Ltd,  Hwaseong-gun (KR)  ( *)  Notice:  Subject to any disclaimer, the term ofthis  patent is extended or adjusted under 35  U.S.C. 154(b) by 204 days.  This patent is subject to a terminal dis› claimer.  (21)  Appl. No.:  11/572,404  (22)  PCT Filed:  Jun.23,2005  (86)  PCT No.:  PCT /KR2005/001955  § 371 (c)(l),  (2), ( 4) Date:  Jan.19,2007  (51)  Int. Cl.  C07D 307102  (2006.01)  (52)  U.S. Cl.  ......................................................  549/477  (58)  Field of Classification Search  ....................... None  See application file for complete search history.  8 Claims, No Drawings  (65)  Prior Publication Data  (30)  Foreign Application Priority Data  (57)  ABSTRACT  OTHER PUBLICATIONS  (56)  References Cited  U.S. PATENT DOCUMENTS  4,526,988  A  7/1985 Hertel  4,965,374  A  10/1990 Chou et al.  5,223,608  A  6/1993 Chou et al.  5,401,861 A  3/1995 Chou et al.  5,428,176  A  6/1995 Weigel  5,434,254  A  7/1995 Chou et al.  5,453,499  A  9/1995 Chou et al.  5,618,951 A  4/1997 Britton  5,945,547  A  8/1999 Chou et al.  3R-carboxylate enantiomer derivative of formula (III) can be  prepared easily and selectively by the method of the present  invention, and a highly pure D-erythro-2,2-difluoro-2-deoxy› l-oxoribose derivative can be prepared efficiently from the  compound of formula (III) as an intermediate.  Primary Examiner-Shaojia  Anna Jiang  Assistant Examiner-Layla  Bland  (74)  Attorney, Agent, or Firm-Sughrue  Mion, PLLC  * cited by examiner  Corey et al. Journal of the American Chemical Society 93:6, Mar. 24,  1971, pp. 1491-1493.*  Greene et al. Protective Groups in Organic Synthesis, Third Edition.  John Wily & Sons, 1999, pp. 150-160.*  US007638642B2  Jul. 23, 2004  (KR)  ...................... 10-2004-0057711  US 2008/0058509 Al  Mar. 6, 2008  (87)  PCT Pub. No.:  WO2006/009353  PCT Pub. Date:  Jan. 26, 2006 