Methyl iodide → HCID 86699127, compound

Temperature

-78 °C

To a solution of hexamethyldisilazane (88 mL, 0.421 mol), in THF (500 mL) at −30° C. was added BuLi (2.5M in hexanes, 169 mL, 0.423 mol) and the mixture stirred at this temperature for 15 minutes before cooling to −78° C. A solution of dimethyl N-(tert-butoxycarbonyl)-L-aspartate (Preparation 70, 50 g, 0.19 mol) in THF (200 mL) was added slowly over 15 minutes and the reaction stirred at −78° C. for 2 hours. MeI (14.3 mL, 0.23 mol) was added over 30 minutes and the reaction continued stirring at −78° C. for 18 hours. The reaction was quenched by pouring into an aqueous solution of KHSO4 (80 g in 600 mL, pH=3). THF was then removed in vacuo and the product extracted into EtOAc. The organic layer was collected, washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified using silica gel column chromatography eluting with 0-10% EtOAc in heptane to afford the title compound as a mixture of diastereomers in a ratio 7:3.

1. stirringthe reaction stirred at −78° C. for 2 hours
2. stirringthe reaction continued stirring at −78° C. for 18 hours
3. customThe reaction was quenched
4. additionby pouring into an aqueous solution of KHSO4 (80 g in 600 mL, pH=3)
5. customTHF was then removed in vacuo
6. extractionthe product extracted into EtOAc
7. customThe organic layer was collected
8. washwashed with brine
9. dry with materialdried over Na2SO4
10. concentrationconcentrated in vacuo
11. customThe residue was purified
12. washeluting with 0-10% EtOAc in heptane

ORD record

ord-5326025b3379472897399312ce5667be

Source dataset

uspto-grants-2015_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08927587B2