Triethylamine → HCID 10847958, compound

Ethyl chloroformate (12.6 mL, 0.13 mol) was added dropwise to a solution of I-Me-Boc-L-Val-OH (27.3 g, 0.12 mol) and triethylamine (14.7 mL, 0.13 mol) in anhydrous THF (200 mL) at −20° C. over 15 min, and the resulting white suspension was stirred further for 30 min. A diazomethane solution (0.36 mol, prepared from 60 g of N-nitroso-N-methylurea and dried over potassium hydroxide) in ether (500 mL), was then introduced into the reaction mixture via cannula. The mixture was allowed to warm to room temperature and stirred for further 5 hours, then carefully quenched with aqueous acetic acid (10%, 250 mL). The layers were separated, and the organic layer was washed with saturated sodium bicarbonate (300 mL×3) and brine (300 mL×3), dried (Na2SO4), concentrated to about 200 mL. The residue was dissolved in THF (900 mL) and water (100 mL). The solution was heated to 40° C., and silver acetate (500 mg) was added. The suspension was stirred for 5 hours, then concentrated to about 300 mL. The residue was extracted with EtOAc (500 mL×3). The organic layer was washed with saturated sodium bicarbonate (300 mL×3) and brine (300 mL), dried (Na2SO4), concentrated to give (R)-3-(tert-butoxycarbonyl(methyl)amino)-4-methylpentanoic acid (23.8 g, 81% yield) which was used in the next step without further purification. 1H NMR (300 MHz, CDCl3): δ 10.08 (bs, 1H), 4.00 (m, 1H), 2.75 (m, 3H), 2.55 (m, 2H), 1.43 (s, 9 h), 0.85-0.84 (m, 6H).

1. stirringstirred for further 5 hours
2. customcarefully quenched with aqueous acetic acid (10%, 250 mL)
3. customThe layers were separated
4. washthe organic layer was washed with saturated sodium bicarbonate (300 mL×3) and brine (300 mL×3)
5. dry with materialdried (Na2SO4)
6. concentrationconcentrated to about 200 mL
7. dissolutionThe residue was dissolved in THF (900 mL)
8. temperatureThe solution was heated to 40° C.
9. additionsilver acetate (500 mg) was added
10. stirringThe suspension was stirred for 5 hours
11. concentrationconcentrated to about 300 mL
12. extractionThe residue was extracted with EtOAc (500 mL×3)
13. washThe organic layer was washed with saturated sodium bicarbonate (300 mL×3) and brine (300 mL)
14. dry with materialdried (Na2SO4)
15. concentrationconcentrated

ORD record

ord-790836770bfa407b80c65c29e84f0c9e

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09427479B2