Diisopropylamine → (+)-3-(Benzyloxy)-6(8-hydroxy-1,4-dioxaspiro[4.5]dec-8-yl)-2-cyclohexen-1-one

Temperature

-78 °C

To a round bottomed flask equipped with magnetic stirrer was added anhydrous tetrahydrofuran (600 ml) and diisopropylamine (38.1 ml, 272 mmol). The stirred solution was cooled to −78° C. and n-butyl lithium (113.4 ml, 272 mmol, 2.4 M in hexanes) was added dropwise via syringe in 20 ml portions. The resulting yellow solution was stirred for 35 min at −78° C., then 3-(benzyloxy)-2-cyclohexen-1-one (50.0 g, 248 mmol) was added as a solution in anhydrous tetrahydrofuran (100 ml). The solution was stirred for 1 hr prior to the addition of cyclohexane-1,4-dione monoethylene ketal (38.7 g, 248 mmol) as a solution in anhydrous tetrahydrofuran (100 ml). The solution was stirred for 2 hr at −78° C., then allowed to warm slowly to room temperature over 1 hr. Saturated aqueous ammonium chloride (80 ml) was added, followed by dichloromethane (700 ml) and the mixture was stirred until no solids remained. The layers were separated and the aqueous phase extracted with dichloromethane (2×100 ml). The combined organic layers were washed with brine (50 ml), dried over magnesium sulfate, then concentrated in vacuo. Trituration of the resulting solid with methanol afforded the title compound (78.4 g, 88%). m/z (ES+) 359 (M+H+).

1. customTo a round bottomed flask equipped with magnetic stirrer
2. stirringThe solution was stirred for 1 hr
3. stirringThe solution was stirred for 2 hr at −78° C.
4. temperatureto warm slowly to room temperature over 1 hr
5. stirringthe mixture was stirred until no solids
6. customThe layers were separated
7. extractionthe aqueous phase extracted with dichloromethane (2×100 ml)
8. washThe combined organic layers were washed with brine (50 ml)
9. dry with materialdried over magnesium sulfate
10. concentrationconcentrated in vacuo

ORD record

ord-00a29384fd7c4361a9350543310fcdeb

Source dataset

uspto-grants-2005_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06861564B2