Hydrochloric Acid → HCID 66819849, compound

Temperature

0 °C

In a flame dried round-bottomed flask equipped with a magnetic stir bar and under inert atmosphere (N2), to a solution of 2-(2-aminoethoxy)ethanol (536 mg, 5.00 mmol) in THF (3 mL) was added aq. 2M NaOH (2.6 mL, 5.20 mmol) at 0° C. The reaction mixture was stirred at 0° C. for 10 min and a solution of di-tert-butyl dicarbonate (1.16 g, 5.20 mmol) in THF (3 mL) was then added dropwise. The reaction mixture was warmed to rt and stirred at this temperature until completion of the reaction. The mixture was diluted with CH2Cl2, filtered and the layers separated. The organic layer was dried over Na2SO4, filtered, and the solvents were removed under reduced pressure. The crude alcohol was redissolved in dry CH2Cl2 (20 mL) and treated with triphenylphoshine on polystyrene (5.63 mmol) and imidazole (190 mg, 2.76 mmol). To this mixture cooled to 0° C. was added iodine (808 mg, 3.15 mmol). The reaction mixture was warmed to rt and stirred at this temperature until completion of the reaction. The mixture was then filtered, CH2Cl2 removed under reduced pressure. The residue was redissolved in EA, successively washed with 10% aq. Na2SO3 and brine, dried over Na2SO4, filtered and concentrated under reduced pressure. The crude iodide was redissolved in CH3CN (15 mL) and treated with pyrrolidine (0.17 mL, 1.99 mmol) and K2CO3 (465 mg, 3.36 mmol). The reaction mixture was stirred at rt until completion of the reaction, filtered and concentrated under reduced pressure. The amine was purified by FC (hept-EA-acetone, 1:0:0->0:0:1) and then the Boc group was removed by treatment with HCl (4.0 M in dioxane, 10 eq.) in dry CH2Cl2 (3 mL). The title compound was obtained after trituration in hot EA/acetone/MeOH as a beige solid. LC-MS-conditions 01: tR=0.13 min; [M+H]+=159.11.

1. temperatureThe reaction mixture was warmed to rt
2. stirringstirred at this temperature until completion of the reaction
3. filtrationfiltered
4. customthe layers separated
5. dry with materialThe organic layer was dried over Na2SO4
6. filtrationfiltered
7. customthe solvents were removed under reduced pressure
8. dissolutionThe crude alcohol was redissolved in dry CH2Cl2 (20 mL)
9. temperatureTo this mixture cooled to 0° C.
10. temperatureThe reaction mixture was warmed to rt
11. stirringstirred at this temperature until completion of the reaction
12. filtrationThe mixture was then filtered
13. customCH2Cl2 removed under reduced pressure
14. dissolutionThe residue was redissolved in EA
15. washsuccessively washed with 10% aq. Na2SO3 and brine
16. dry with materialdried over Na2SO4
17. filtrationfiltered
18. concentrationconcentrated under reduced pressure
19. dissolutionThe crude iodide was redissolved in CH3CN (15 mL)
20. stirringThe reaction mixture was stirred at rt until completion of the reaction
21. filtrationfiltered
22. concentrationconcentrated under reduced pressure
23. customThe amine was purified by FC (hept-EA-acetone, 1:0:0->0:0:1)

ORD record

ord-54c439b5bf1d4735bb72f3b590e69467

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08563714B2