Hydrochloric Acid → HCID 86635428, Verbindung

Temperatur

60 °C

To a solution of 4-methanesulfonyloxy-piperidine-1-carboxylic acid tert-butyl ester (Ex. 3a, 35.5 g, 0.13 moles) in degassed 2-butanone (400 mL) were added 2,6-di-tert-butyl-4-mercapto-phenol (37.9 g, 0.16 moles) and cesium carbonate (62.7 g, 0.19 moles). The resulting solution was heated to 60° C. and stirred for 8 hours. Upon completion, as determined by HPLC, the reaction was diluted with 400 mL water and 500 mL ethyl acetate. The layers were cut and the organic layer was washed with saturated ammonium chloride solution (400 mL) and brine (400 mL). The volume was then concentrated under reduced pressure to 250 mL. 1,4-Dioxane (300 mL) was added, and then concentrated under reduced pressure to 100 mL. 1,4-Dioxane (300 mL) was added again. HCl (4.0 M in dioxane, 195 mL, 0.7 moles) was added slowly over 30 minutes, and the reaction was stirred at room temperature for 16 hours. The solution was concentrated under reduced pressure to 100 mL, and 1:3 solution of ethyl acetate:hexanes (250 mL) was added while stirring. After 3 hours, the solid was filtered and rinsed with a 1:9 solution of Ethyl acetate:hexanes (80 mL). The wet cake was allowed to air dry, and the solid were added to 120 mL of ethyl acetate and 120 mL of water. A 5.0 N solution of NaOH (28 mL, 0.14 moles) was added to the solution and the reaction was stirred for 30 minutes. The layers were cut. The organic layer was washed with a 6% brine solution (2×100 mL). The solution was concentrated under reduced pressure, and hexanes (70 mL) was added. The mixture was stirred for 16 hours at room temperature, then cooled to −5° C. and stirred for another hour. The solution was filtered and the solid was rinsed with cold hexanes (15 mL) and dried in a vacuum oven for 16 hours, affording 29.5 g (72.2%) of 2,6-di-tert-butyl-4-(piperidin-4-ylsulfanyl)-phenol as a white solid, mp 113-114° C. 1H-NMR (400 MHz, CDCl3): δ7.28 (s, 2H), 5.27 (s, 1H), 3.14-3.09 (m, 2H), 2.98-2.91 (m, 1H), 2.66-2.59 (m, 2H), 1.96-1.92 (m, 2H), 1.51-1.47 (m, 2H), 1.44 (s, 18H). HRMS (ESI) Calcd. for C19H31NOS: 322.2204 ([M+H]+). Found: 322.2196. Anal. Calcd. for C19H31NOS, C, 70.98; H, 9.72; N, 4.36; S, 9.97. Found: C, 70.87; H, 9.76; N, 4.30; S, 9.93.

1. washthe organic layer was washed with saturated ammonium chloride solution (400 mL) and brine (400 mL)
2. concentrationThe volume was then concentrated under reduced pressure to 250 mL
3. addition1,4-Dioxane (300 mL) was added
4. concentrationconcentrated under reduced pressure to 100 mL
5. addition1,4-Dioxane (300 mL) was added again
6. stirringthe reaction was stirred at room temperature for 16 hours
7. concentrationThe solution was concentrated under reduced pressure to 100 mL, and 1:3 solution of ethyl acetate
8. additionhexanes (250 mL) was added
9. stirringwhile stirring
10. waitAfter 3 hours
11. filtrationthe solid was filtered
12. washrinsed with a 1:9 solution of Ethyl acetate
13. customto air dry
14. additionthe solid were added to 120 mL of ethyl acetate and 120 mL of water
15. stirringthe reaction was stirred for 30 minutes
16. washThe organic layer was washed with a 6% brine solution (2×100 mL)
17. concentrationThe solution was concentrated under reduced pressure, and hexanes (70 mL)
18. additionwas added
19. stirringThe mixture was stirred for 16 hours at room temperature
20. temperaturecooled to −5° C.
21. stirringstirred for another hour
22. filtrationThe solution was filtered
23. washthe solid was rinsed with cold hexanes (15 mL)
24. customdried in a vacuum oven for 16 hours

ORD-Eintrag

ord-88e2e865a67c4da1a0bbabbeb96c0e2d

Quelldatensatz

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07897776B2