Bromoacetonitrile → HCID 117608159, compound

Temperature

-78 °C

To a solution of Boc-Glu(OMe)-OMe (20.0 g., 72.6 mmol) in THF (50 mL) was added dropwise a solution of LiHMDS (26.3 g, 157 mmol) in THF (250 mL) at −78° C. under nitrogen atmosphere. The mixture was stirred at −78° C. for 1.5 h and bromoacetonitrile (13.0 g, 108 mmol) was added dropwise over 1 h while maintaining the temperature below −70° C. The reaction mixture was stirred at −78° C. for 2 h and quenched with pre-cooled methanol (10 mL) in one portion. The mixture was stirred for 10 min and then treated with a pre-cooled solution of acetic acid (9 mL) in THF (60 mL). The mixture was stirred for 10 min and poured into brine (200 mL). The resulting mixture was extracted with EtOAc (300 mL×2) and the combined extracts were dried over anhydrous sodium sulfate and concentrated under reduced pressure. The residue was purified by flash column chromatography on silica gel (heptanes/EtOAc=1:1) to afford (2S)-dimethyl 2-((tert-butoxycarbonyl)amino)-4-(cyanomethyl)pentanedioate (16.0 g, 70% yield) as a light brown oil.

1. temperaturewhile maintaining the temperature below −70° C
2. stirringThe reaction mixture was stirred at −78° C. for 2 h
3. customquenched with pre-cooled methanol (10 mL) in one portion
4. stirringThe mixture was stirred for 10 min
5. additiontreated with a pre-cooled solution of acetic acid (9 mL) in THF (60 mL)
6. stirringThe mixture was stirred for 10 min
7. additionpoured into brine (200 mL)
8. extractionThe resulting mixture was extracted with EtOAc (300 mL×2)
9. dry with materialthe combined extracts were dried over anhydrous sodium sulfate
10. concentrationconcentrated under reduced pressure
11. customThe residue was purified by flash column chromatography on silica gel (heptanes/EtOAc=1:1)

ORD record

ord-f9a591953073473fbda4fc43fe2c30c2

Source dataset

uspto-grants-2016_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09434761B2