Diisopropylamine → Dibenzyl 2-isopropyl-2-hydroxy-3-methylsuccinate

Temperature

-78 °C

To anhydrous tetrahydrofuran (5 mL) was added diisopropylamine (759 mg, 7.5 mmol) under nitrogen stream, and the mixture was cooled to −78° C. To the solution was added a 1.58 M n-butyl lithium-hexane solution (4.3 mL, 6.8 mmol), and the mixture was stirred at −78° C. for 5 min, and then at 0° C. for 15 min. The solution of lithium diisopropylamide tetrahydrofuran was cooled to −78° C., and a solution of benzyl propionate (821 mg, 5.0 mmol) in anhydrous tetrahydrofuran (10 mL) was added dropwise over 1 h, and the reaction mixture was further stirred at −78° C. for 1 h. The enolate thus prepared was added via a cannula to a solution of benzyl 3-methyl-2-ketobutyrate (1.24 g, 6.0 mmol) in anhydrous tetrahydrofuran (5 mL) having been cooled to −78° C. After stirring at −78° C. for 2 h, the reaction mixture was diluted with a 10% aqueous citric acid solution, and extracted with ethyl acetate. The organic layer was washed with 1 M hydrochloric acid, saturated aqueous sodium hydrogen carbonate and brine, dried over anhydrous magnesium sulfate, and filtered. The solvent was evaporated under reduced pressure, and the residue thus obtained was subjected to silica gel column chromatography (hexane-ethyl acetate 9:1) to give 1.22 g of dibenzyl 2-isopropyl-2-hydroxy-3-methylsuccinate as oil (yield: 66%) in the form of a diastereomer mixture.

1. additionTo the solution was added a 1.58 M n-butyl lithium-hexane solution (4.3 mL, 6.8 mmol)
2. waitat 0° C. for 15 min
3. stirringthe reaction mixture was further stirred at −78° C. for 1 h
4. temperaturehaving been cooled to −78° C
5. stirringAfter stirring at −78° C. for 2 h
6. extractionextracted with ethyl acetate
7. washThe organic layer was washed with 1 M hydrochloric acid, saturated aqueous sodium hydrogen carbonate and brine
8. dry with materialdried over anhydrous magnesium sulfate
9. filtrationfiltered
10. customThe solvent was evaporated under reduced pressure
11. customthe residue thus obtained

ORD record

ord-c3bfdbfb56dc4b4691b441743fe77d2b

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09260375B2