Allyl bromide → diisopropyl (2R,3S)-2-allyl-3-hydroxybutanedioate

Temperature

-78 °C

To a cold (−78° C.) solution of diisopropyl (S)-(−)-malate (4.74 mL; 22.9 mmol; 1.0 eq.) in anhydrous THF (8.50 mL) was slowly added under argon lithium bis(trimethylsilyl)amide (48.1 mL; 1.0 M in THF; 48.11 mmol; 2.1 eq.) keeping the temperature below −66° C. After 45 min of addition, the reaction mixture was stirred at −78° C. for 2 h, then the temperature of the reaction mixture was allowed to reach 11° C. After 1 h at that temperature, the mixture was cooled at −78° C. and allyl bromide (2.9 mL; 34.4 mmol; 1.5 eq.) was added. The solution was stirred overnight allowing the temperature to reach RT. The reaction was then quenched with ice water and an aqueous saturated solution of NH4Cl. The aqueous layer was extracted 3 times with EtOAc and the combined organic layers were washed with a saturated solution of NaCl, dried over MgSO4 and evaporated to obtain an orange oil (5.4 g). Purification by chromatography (SiO2, 10/90 EtOAc/c-hex) gave the title product as a colorless oil (3.05 g, 51.5%). 1H NMR (CDCl3, 300 MHz) δ 5.76-5.59 (m, 1H), 5.07-4.80 (m, 4H), 4.08 (d, J=2.3 Hz, 1H), 3.03 (br s, 1H), 2.80-2.72 (m, 1H), 2.53-2.41 (m, 1H), 2.34-2.21 (m, 1H), 1.14 (d, J=6.4 Hz, 6H), 1.07 (d, J=6.4 Hz, 6H).

1. customthe temperature below −66° C
2. additionAfter 45 min of addition
3. customto reach 11° C
4. waitAfter 1 h at that temperature
5. temperaturethe mixture was cooled at −78° C.
6. stirringThe solution was stirred overnight
7. customto reach RT
8. customThe reaction was then quenched with ice water
9. extractionThe aqueous layer was extracted 3 times with EtOAc
10. washthe combined organic layers were washed with a saturated solution of NaCl
11. dry with materialdried over MgSO4
12. customevaporated

ORD record

ord-109c94e89c8940a89de8877da757fd10

Source dataset

uspto-grants-2011_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08008302B2