Water → (5R,6S)-1,1-diisopropoxy-5-hydroxy-2,2,6-trimethyl-8-nonen-3-one

Temperature

-78 °C

A solution of 1,1-diisopropoxy-2,2,-dimethyl-3-butanone (3.08 g) in 15 mL of ether is added slowly to a solution of lithium diisopropylamide (15.7 mmol) in 20 mL of ether cooled to −78° C., the mixture is stirred for 30 minutes, warmed to −40° C. and stirred for 30 minutes, then recooled to −78° C. A solution of bis(1,2:5,6-di-O-isopropylidene-α-D-glucofuranos-3-O-yl)cyclopentadienyltitanium chloride (17.4 mmol) in 180 mL of ether is added dropwise over 40 minutes, and the reaction is stirred for an additional 30 minutes at −78° C., warmed to −30° C. and kept for 45 minutes, then recooled to −78° C. A solution of (2S)-2-methyl-4-pentenal (16.36 mmol) in 30 mL of ether is added over 10 minutes and the mixture is stirred for 2 hours at −78° C. A 5 M solution of water in THF (28 mL) is added, the mixture is stirred for 1 hour and then filtered through Celite. The filtrate is washed with sat. aq. NaCl, and the brine layer is back extracted with ether. The organic phases are combined, dried with Na2SO4, filtered, and evaporated. The product is purified by chromatography on SiO2.

1. temperaturewarmed to −40° C.
2. stirringstirred for 30 minutes
3. customrecooled to −78° C
4. stirringthe reaction is stirred for an additional 30 minutes at −78° C.
5. temperaturewarmed to −30° C.
6. waitkept for 45 minutes
7. customrecooled to −78° C
8. stirringthe mixture is stirred for 2 hours at −78° C
9. stirringthe mixture is stirred for 1 hour
10. filtrationfiltered through Celite
11. washThe filtrate is washed with sat. aq. NaCl
12. extractionthe brine layer is back extracted with ether
13. dry with materialdried with Na2SO4
14. filtrationfiltered
15. customevaporated
16. customThe product is purified by chromatography on SiO2

ORD record

ord-1535afc4db5e497e8974cff423c6cddd

Source dataset

uspto-grants-2005_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06893859B2