Triethylamine → HCID 19166803, compound

(±)-Alanine methyl ester hydrochloride salt (35.2 g, 280 mmol) and Et3N (58.5 ml, 420 mmol) were sequentially added to a stirred solution of nicotinoyl chloride (19.8 g, 140 mmol) in acetonitrile (800 mL) and stirred at ambient temperature for 10 min and then 80° C. for 2 h. The reaction mixture was poured into a separatory funnel containing brine and ethyl acetate. The biphasic mixture was separated, and the organic layer was washed one time with brine, dried over MgSO4, filtered and concentrated to dryness. The crude product was triturated in 80% ethyl acetate/hexanes overnight at ambient temperature. The solids were removed by filtration over Celite® and the filtrate was concentrated in vacuo to give the desired product as a clear brown oil (20 g, 69%): 1H NMR (300 MHz, CDCl3) δ 9.04 (d, J=2.2 Hz, 1H), 8.75 (dd, J=4.9, 1.4 Hz, 1H), 8.13 (dt, J=7.7, 1.9 Hz, 1H), 7.40 (dd, J=8.0, 4.9 Hz, 1H), 6.92 (br s, 1H), 4.82 (m, 1H), 3.81 (s, 3H), 1.55 (d, J=7.1 Hz, 3H); ESIMS m/z 209 (M+1), m/z 207 (M−1).

1. wait80° C. for 2 h
2. additionThe reaction mixture was poured into a separatory funnel
3. customThe biphasic mixture was separated
4. washthe organic layer was washed one time with brine
5. dry with materialdried over MgSO4
6. filtrationfiltered
7. concentrationconcentrated to dryness
8. customThe crude product was triturated in 80% ethyl acetate/hexanes overnight at ambient temperature
9. customThe solids were removed by filtration over Celite®
10. concentrationthe filtrate was concentrated in vacuo

ORD record

ord-05cb4acf1faf4e91bd543309a6a426f4

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08853246B2