Acetonitrile → (3aR,4R,5R,6aS)-Hexahydro-5-hydroxy-4-[(3R)-5-phenyl-3-[(tetrahydro-2H-pyran-2-yl)oxy]pentyl]-2H-cyclopenta[b]furan-2-ol

A 1.5 M solution of Diisobutylaluminum hydride in toluene (46.0 g, 69 mmol) was added dropwise to a stirred solution of compound [9a] (17.0 g, 30 mmol) in toluene (500 mL) at −20-−10° C. The mixture was stirred for 1 hour at the same temperature. Methanol (200 mL) was added dropwise to the stirred mixture at −20-−10° C. The obtained mixture was stirred for 1 hour at room temperature, filtered and evaporated under reduced pressure. Dichloromethane (250 mL) was added to the residue. The resulting solution was washed with brine (2×220 mL), dried over sodium sulfate, filtered and evaporated under reduced pressure. To complete hydrolysis of p-phenylbenzoate-groups a mixture of the residue and potassium carbonate (10:0 g) in methanol (100 mL) was stirred at room temperature for 7 hours (TLC monitoring). The mixture was evaporated under reduced pressure. A mixture of the residue, dichloromethane (300 mL) and water (300 mL) was stirred for 10 min at room temperature. The organic layer was separated, washed with brine, dried over sodium sulfate, filtered and evaporated under reduced pressure. The residue was purified by column chromatography on silica gel exane/ethyl acetate 1:2 v/v) to obtain 10.3 g of the compound [11a] (88% yield), [α]D20 −53.5° (c 1.0, MeCN). 1H NMR (CDCl3) δ: 7.10-7.29 (m, 5H); 5.47-5.63 (m, 1H); 4.57-4.69 (m, 2H); 3.69-3.94 (m, 2H); 3.60-3.75 (m, 1H); 3.40-3.55 (m, 1H). 13C NMR (CDCl3) δ: 19.9; 25.4; 29.0; 31.2; 31.9; 36.6; 40.2; 41.5; 42.5; 46.4; 48.0; 55.3; 55.6; 62.8; 79.4; 79.9; 82.4; 86.4; 97.6; 100.0; 101.1; 125.6; 128.2; 128.3; 142.5. IR (neat): 3398, 2944, 2867, 1451 cm−1.

1. stirringThe obtained mixture was stirred for 1 hour at room temperature
2. filtrationfiltered
3. customevaporated under reduced pressure
4. additionDichloromethane (250 mL) was added to the residue
5. washThe resulting solution was washed with brine (2×220 mL)
6. dry with materialdried over sodium sulfate
7. filtrationfiltered
8. customevaporated under reduced pressure
9. customTo complete hydrolysis of p-phenylbenzoate-groups
10. stirringwas stirred at room temperature for 7 hours (TLC monitoring)
11. customThe mixture was evaporated under reduced pressure
12. additionA mixture of the residue, dichloromethane (300 mL) and water (300 mL)
13. stirringwas stirred for 10 min at room temperature
14. customThe organic layer was separated
15. washwashed with brine
16. dry with materialdried over sodium sulfate
17. filtrationfiltered
18. customevaporated under reduced pressure
19. customThe residue was purified by column chromatography on silica gel exane/ethyl acetate 1:2 v/v)

ORD record

ord-8acf622d93d4432dbe98fa701efd0381

Source dataset

uspto-grants-2005_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06927300B2