Sodium Hydroxide → (4R,6S,E)-6-[2-[4,5-Bis(4-fluorophenyl)-2-(1-methylethyl)-1H-imidazol-1-yl]-ethenyl]-4-hydroxy-tetrahydro-2H-pyran-2-one

A solution of 1,1-dimethyleth-1-yl (3R,5S,E)-7-[4,5-bis(4-fluorophenyl)-2-(1-methylethyl)-1H-imidazol-1-yl]-3,5-dihydroxy-6-heptenoate (25.6 mg) in redistilled THF (1.4 ml) was treated with aqueous sodium hydroxide solution (0.1M, 0.5 ml) and the clear colourless solution was stirred at room temperature. After 3.5 h the reaction mixture was concentrated to ca 0.5 ml. The residue was diluted with water (3 ml), acidified to pH 4 with hydrochloric acid (2M), ammonium sulphate added and then extracted with ethyl acetate (4×3 ml). The combined extracts were dried and evaporated to a white gummy solid (25 mg). This was dissolved in dry dichloromethane (1.4 ml) and then treated with 1-cyclohexyl-3-(2-morpholinoethyl)carbodiimide metho-p-toluenesulphonate (42.4 mg). The resulting solution was stirred at room temperature. After 18.5 h the reaction mixture was diluted with water (5 ml) and then extracted with dichloromethane (3×5 ml). The combined extracts were washed with brine (5 ml), dried and evaporated to a cream solid (23 mg). The solid was filtered through a short column of 70-230 mesh silica developing and eluting with System A (3:1) to give the title compound as a cream solid (18 mg), νmax (CHBr3) 1735 cm-1 (lactone), δ(CDCl3) values as for those described for the racemate obtained in Example 10.

1. concentrationAfter 3.5 h the reaction mixture was concentrated to ca 0.5 ml
2. additionThe residue was diluted with water (3 ml)
3. additionadded
4. extractionextracted with ethyl acetate (4×3 ml)
5. customThe combined extracts were dried
6. customevaporated to a white gummy solid (25 mg)
7. dissolutionThis was dissolved in dry dichloromethane (1.4 ml)
8. additiontreated with 1-cyclohexyl-3-(2-morpholinoethyl)carbodiimide metho-p-toluenesulphonate (42.4 mg)
9. stirringThe resulting solution was stirred at room temperature
10. additionAfter 18.5 h the reaction mixture was diluted with water (5 ml)
11. extractionextracted with dichloromethane (3×5 ml)
12. washThe combined extracts were washed with brine (5 ml)
13. customdried
14. customevaporated to a cream solid (23 mg)
15. filtrationThe solid was filtered through a short column of 70-230 mesh silica developing
16. washeluting with System A (3:1)

ORD record

ord-eee6d6c03e5d4e1780b481aaa8146d7e

Source dataset

uspto-grants-1991_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05013749