Diisopropylamine → HCID 69083807, compound

Temperature

-15 °C

In a flame dried flask under nitrogen was added diisopropylamine (0.976 mL, 6.85 mmol), tetrahydrofuran (4 mL) and the vessel was cooled to −78° C. n-BuLi (2.74 mL, 6.85 mmol) was added dropwise and after 10 min, the reaction was warmed to −15° C. and held there for 10 min before recooling to −78° C. 2-(5-bromopyridin-3-yl)propanoic acid (750 mg, 3.26 mmol) held in a flame dried flask was dissolved in tetrahydrofuran (4 mL) and added dropwise to the preformed LDA resulting in a kool-aid orange solution. The ice bath was again removed and the reaction was allowed to stir at ambient temperature for 1.5 h, recooled to −78° C. and 2,5-difluorobenzaldehyde (0.779 mL, 7.17 mmol) in 2 mL tetrahydrofuran was added over 10 min. After 1 h, the reaction was quenched with 10% citric acid and the volatiles were removed under vacuum. The residue was extracted with 3 portions ether, washed with brine, dried over MgSO4, filtered and concentrated to 1.31 g red gum which was used immediately in the next step.

1. customIn a flame dried flask under nitrogen
2. additionwas added dropwise and after 10 min
3. custombefore recooling to −78° C
4. customdried flask
5. dissolutionwas dissolved in tetrahydrofuran (4 mL)
6. additionadded dropwise to the preformed LDA resulting in a kool-aid orange solution
7. customThe ice bath was again removed
8. customrecooled to −78° C.
9. waitAfter 1 h
10. customthe reaction was quenched with 10% citric acid
11. customthe volatiles were removed under vacuum
12. extractionThe residue was extracted with 3 portions ether
13. washwashed with brine
14. dry with materialdried over MgSO4
15. filtrationfiltered
16. concentrationconcentrated to 1.31 g red gum which

ORD record

ord-f0f7b9fec7ef41c9af0ac2b6f048e802

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691821B2