Methyl iodide → Diisopropyl (2R,3S)-2-hydroxy-3-methylsuccinate

Temperature

20 °C

To a cold (−78° C.) solution of diisopropyl-(S)-(−)-malate (4.72 mL, 22.9 mmol, 1 eq.) in anhydrous THF (8.50 mL) was added slowly a solution (1 M) of lithium bis(trimethylsilyl)amide (48.1 mL, 48.1 mmol, 2.10 eq.) in THF. The temperature was raised to 20° C. over 30 minutes, than lowered again to −78° C. Iodomethane (1.7 mL, 28 mmol, 1.20 eq.) was added and the mixture stirred at RT for 16 hours. The reaction mixture was then cooled to 0° C. and a saturated solution of NH4Cl was added. The resulting mixture was diluted with water, extracted three times with EtOAc. The combined organic phases were washed with brine, dried over MgSO4, filtered and evaporated under reduced pressure. The residue was then purified by chromatography (SiO2, 20/80 EtOAc/c-hex) to give the product (mixture of diastereoisomers) as a colourless oil (3.77 g, 71%).

1. customthan lowered again to −78° C
2. temperatureThe reaction mixture was then cooled to 0° C.
3. extractionextracted three times with EtOAc
4. washThe combined organic phases were washed with brine
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. customevaporated under reduced pressure
8. customThe residue was then purified by chromatography (SiO2, 20/80 EtOAc/c-hex)
9. customto give

ORD record

ord-330ce10bbb9742779334e24660112c9d

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08008302B2