Claims
- 1. A process of synthesizing a compound of formula 1: ##STR15## wherein P and P' independently represent H or a protecting group, R.sub.1 represents H or C.sub.1-4 alkyl, and Hal represents a halogen selected from the group consisting of F, Cl, Br and I, comprising:
- reacting a compound of formula 2: ##STR16## wherein P, P', and R.sub.1 are defined above, with an alcohol of the formula, R.sub.2 OH, wherein R.sub.2 is C.sub.1-4 alkyl, C.sub.6-10 aryl or C.sub.5-10 heteroaryl in the presence of an acid catalyst or carbodimide reagent to produce a compound of formula 3: ##STR17## wherein P, P', and R.sub.1 are defined above; and reacting a compound of formula 3 in the presence of a base and a haloalkylating agent selected from the group consisting of ICH.sub.2 Cl, BrCH.sub.2 Cl, TMSCH.sub.2 Cl, and TMSCH.sub.2 Br, wherein TMS is trimethylsilyl, to produce a compound of formula 1.
- 2. A process of synthesizing a compound of formula 1: ##STR18## wherein: P and P' independently represent trimethylsilyl, triethylsilyl or t-butyldimethylsilyl;
- R.sub.1 represents H or methyl;
- and Hal represents Cl, Br or I;
- comprising:
- reacting a compound of formula 2: ##STR19## wherein P, P' and R.sub.1 are defined above, with R.sub.2 OH, wherein R.sub.2 OH is methanol, ethanol, propanol or isopropanol; in the presence of 1-hydroxybenzotriazole hydrate, DCC, or EDC to produce a compound of formula 3: ##STR20## wherein P, P', and R.sub.1 are defined above; and reacting a compound of formula 3 in the presence of MeLi and ICH.sub.2 Cl, or s-BuLi and TMSCH.sub.2 Cl, to produce a compound of formula 1.
- 3. A process in accordance with claim 1 wherein R.sub.1 is ethyl, ethyl, isopropyl or t-butyl.
- 4. A process in accordance with claim 1 wherein P and P' are independently selected from the group consisting of t-butylmethylphenylsilyl, t-butyldiphenylsilyl, trimethylsilyl, triethylsilyl, t-utyldimethylsilyl, o-nitrobenzyloxycarbonyl, p-nitrobenzyloxycarbonyl, p-nitrobenzyl, benzyloxy-carbonyl, t-butyloxycarbonyl, 2,2,2-trichloroethyloxycarbonyl and allyloxycarbonyl.
- 5. A process in accordance with claim 4 wherein P and P' are independently trimethylsilyl, triethylsilyl or t-butyldimethylsilyl.
- 6. A process in accordance with claim 1 wherein the alcohol is chosen from the group consisting of methanol, ethanol, propanol and isopropanol.
- 7. A process in accordance with claim 1 wherein the acid catalyst is selected from the group consisting of HCl, H.sub.2 SO.sub.4 and 1-hydroxybenzotriazole hydrate.
- 8. A process in accordance with claim 7 wherein the acid catalyst is 1-hydroxybenzotriazole hydrate.
- 9. A process in accordance with claim 1 wherein the the carbodiimide reagent is DCC or EDC.
- 10. A process in accordance with claim 1 wherein the base is selected from the grolip consisting of MeLi, s-BuLi and n-BuLi.
- 11. A process in accordance with claim 10 wherein the base is MeLi and the haloalkylating agent is ICH.sub.2 Cl.
- 12. A process in accordance with claim 10 wherein the base is s-BuLi and the haloalkylating agent is TMSCH.sub.2 Cl.
REFERENCE TO RELATED APPLICATION
This application claims the benefit of U.S. Provisional Application Ser. No. 60/057,353, filed Aug. 25, 1997.
Foreign Referenced Citations (1)
Number |
Date |
Country |
0 451 764 A1 |
Oct 1991 |
EPX |
Non-Patent Literature Citations (2)
Entry |
Shiozaki, Tetrahedron 40(10) 1795, 1984. |
S. M. Schmitt et al. J. Antibiotic, 41(6), p. 780-787 (1988). |