Hydrogen Sulfide → 2-(4-Mercaptopiperidin-1-yl)-2-methylpropionic acid methyl ester

H2S gas was bubbled into a solution of 2-methyl-2-(4-oxopiperidin-1-yl)propionic acid methyl ester (1.28 g, 6.42 mmol) in isopropanol (13 mL) for 10 min. The reaction mixture was then sealed, stirred at RT for 18 h and then left standing for 8 days at RT. After this period of time, nitrogen was bubbled into the solution for 10 min, then NaBH4 (364 mg, 9.63 mmol) was added. The reaction mixture was stirred at RT for 10 min and then heated at 80° C. for 2 h. After cooling to RT, volatiles were removed under reduced pressure and the resulting residue was partitioned between diethyl ether and water. The aqueous layer was further extracted with diethyl ether and the combined organic phases were washed with water, followed by brine, then dried over Na2SO4 and concentrated in vacuo. 2-(4-Mercaptopiperidin-1-yl)-2-methylpropionic acid methyl ester (1.497 g, quantitative yield) was obtained as a colorless oil. 1H NMR (CDCl3, 300 MHz): δ 3.71 (3H, s), 3.01-2.85 (2H, m), 2.82-2.64 (1H, m), 2.33-2.14 (2H, m), 2.06-1.94 (2H, m), 1.71-1.58 (2H, m), 1.53-1.48 (1H, m), 1.29 (6H, s).

1. customThe reaction mixture was then sealed
2. waitleft
3. waitstanding for 8 days at RT
4. customAfter this period of time, nitrogen was bubbled into the solution for 10 min
5. stirringThe reaction mixture was stirred at RT for 10 min
6. temperatureheated at 80° C. for 2 h
7. temperatureAfter cooling to RT
8. customvolatiles were removed under reduced pressure
9. customthe resulting residue was partitioned between diethyl ether and water
10. extractionThe aqueous layer was further extracted with diethyl ether
11. washthe combined organic phases were washed with water
12. dry with materialdried over Na2SO4
13. concentrationconcentrated in vacuo

ORD-Eintrag

ord-afa957beddf54076a8645e24e5240cee

Quelldatensatz

uspto-grants-2015_07

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09090628B2