Hydrochloric Acid → HCID 86643336, compound

Temperature

0 °C

THF (10 ml) and MeOH (8 ml) were added to cis(±)1-tert-butyl 3-methyl 4-{[(3,4-dichloro-5-methyl-1H-pyrrol-2-yl)carbonyl]amino}piperidine-1,3-dicarboxylate (Intermediate 46; 2.24 g). The resultant mixture was cooled to 0° C., and a solution of lithium hydroxide (0.37 g) in water (5 ml) at 0° C. was added dropwise via pipette, producing a clear, lightly yellow solution. The reaction was stirred at 0° C. for 2 h, stored overnight in a freezer without stirring, then stirred again at 0° C. for six hours. The reaction was acidified to pH 3 with 2N HCl 9-7 ml), and was concentrated in vacuo. The resultant mixture was dissolved in EtOAc (125 ml) and a saturated aqueous sodium chloride solution (40 ml), followed by the addition of 2N HCl (˜1 ml) to acidify the aqueous layer to pH 1. The phases were separated and the aqueous layer was washed with EtOAc (2×60 ml). The combined EtOAc layers were dried over anhydrous MgSO4 and concentrated in vacuo. The resultant white solid was suspended in anhydrous THF (35 ml) under an argon atmosphere, cooled to 0° C., followed by the addition of 4 M HCl in 1,4-dioxane (10 ml, 40 mmol). The reaction was warmed to room temperature, producing a clear orange-red solution. The reaction was stirred overnight at room temperature, followed by the addition of 5 ml of 4 M HCl in 1,4-dioxane. The reaction was stirred for two days at room temperature, then heated to 50° C. for two hours, and allowed to slowly cool to room temperature overnight. The reaction was concentrated in vacuo, and carried on to the next reaction without further purification (5.16 mmol). MS (ES)(M+H)): 320, 322 for C12H15Cl2N3O3.

1. customproducing a clear, lightly yellow solution
2. waitstored overnight in a freezer
3. stirringwithout stirring
4. stirringstirred again at 0° C. for six hours
5. concentrationwas concentrated in vacuo
6. dissolutionThe resultant mixture was dissolved in EtOAc (125 ml)
7. additiona saturated aqueous sodium chloride solution (40 ml), followed by the addition of 2N HCl (˜1 ml)
8. customThe phases were separated
9. washthe aqueous layer was washed with EtOAc (2×60 ml)
10. dry with materialThe combined EtOAc layers were dried over anhydrous MgSO4
11. concentrationconcentrated in vacuo
12. temperaturecooled to 0° C.
13. temperatureThe reaction was warmed to room temperature
14. customproducing a clear orange-red solution
15. stirringThe reaction was stirred overnight at room temperature
16. stirringThe reaction was stirred for two days at room temperature
17. temperatureheated to 50° C. for two hours
18. temperatureto slowly cool to room temperature overnight
19. concentrationThe reaction was concentrated in vacuo
20. customcarried on to the next reaction without further purification (5.16 mmol)

ORD record

ord-865a7c31444e48ccada64860b962e772

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08399489B2