Ethanol → Methyl 5-(3-((1R,2R,3R,5R)-2-((3S,7S,E)-7-(tert-butyldimethylsilyloxy)-3-hydroxyoct-1-enyl)-5-chloro-3-(tetrahydro-2H-pyran-2-yloxy)cyclopentyl)propyl)thiophene-2-carboxylate

Temperature

-85 °C

Lithium aluminum hydride (7.5 mL of a 1.0M solution in THF, 7.5 mmol) was added to an oven-dried 200 mL flask. A freshly prepared solution of absolute ethanol (11.9 mL of a 1.0M solution in THF, 7.50 mmol) was added dropwise at 23° C. After 15 min a solution of (S)-(−)-1,1′-binaphthol (2.18 g, 7.62 mmol) in THF (10 mL) was added dropwise. The milky-white solution was cooled to −85° C. and a solution of the enone 14 (1.60 g, 2.50 mmol) in THF (9 mL) was added over a 5-10 min period. The reaction solution was stirred for 1 h and then warmed to −78° C. and allowed to stir an additional 3 h. The reaction was then quenched by careful addition of MeOH (3.1 mL). The reaction was then allowed to warm to room temperature and was extracted with EtOAc (2×). The combined organic portions were washed with 1N HCl, saturated aqueous NaHCO3, and brine. The organic portion was then dried over anhydrous MgSO4), filtered and concentrated in vacuo. FCC (silica gel, 6:1 hex/EtOAc) afforded 1.20 g (75%) of (S)-alcohol 15.

1. temperaturewarmed to −78° C.
2. stirringto stir an additional 3 h
3. customThe reaction was then quenched by careful addition of MeOH (3.1 mL)
4. temperatureto warm to room temperature
5. extractionwas extracted with EtOAc (2×)
6. washThe combined organic portions were washed with 1N HCl, saturated aqueous NaHCO3, and brine
7. dry with materialThe organic portion was then dried over anhydrous MgSO4),
8. filtrationfiltered
9. concentrationconcentrated in vacuo

ORD record

ord-4d5948d4b797438baa6c176c363d34c8

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08546603B2