Sodium Hydroxide → HCID 17932014, compound

Temperature

30 °C

Synthesis of Sodium (5-benzyl 1-tert-butyl 2-(4,7,10-tris(2-tert- butoxy-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)pentanedioate bromide, Compound XIV. 1,4,7,10-Tetraazacyclododecane-1,4,7-triacetic acid, tri-t-butyl ester hydrobromide, 10.0 g (0.0168 mole), was stirred with aqueous sodium hydroxide, 0.1N 150 mL, and diethyl ether, 150 mL. When the entire solid had dissolved, the organic phase was collected and the aqueous phase washed with diethyl ether, 3×50 mL. The combined organic extracts were washed with 1×50 mL saturated aqueous sodium chloride, dried with magnesium sulfate, filtered and evaporated, under reduced pressure, to an oil, 8.8g (0.0171 mole as the free base). The oil was dissolved in acetonitrile, 100 mL. To this solution was added sodium bicarbonate, 1.51 g (0.0180 mole). The mixture was warmed to 30° C. A solution of 5-benzyl, 1-tert-butyl 2-bromopentandioate, 8.02 g (0.0180 mole), in acetonitrile, 40 mL, was added dropwise and the mixture was stirred overnight under argon. The resulting mixture was filtered and the filtrate concentrated under reduced pressure to give a clear colorless oil. The oil was dissolved in diethyl ether, 100 mL, with stirring. The product began crystallizing after a few minutes. After stirring for ca. 1 hr, the product was collected by filtration, washed with fresh ether and vacuum dried. NMR analysis revealed the solid, 9.3g, consisted of a mixture of Na-DO3A-tris (tert-butyl ester) bromide and the desired product. The solid was recrystallized twice from minimal ethyl acetate, ca.,100 mL ea., giving very pure product. The yield was 2.7 g, 18% based on starting 5-benzyl, 1-tern-butyl 2-bromopentandioate. Anal. Calc. As the monohydrate % C, 55.25; H, 7.44; N, 6.08; Br, 9.08; Na, 3.68. Found C, 55.32; H, 7.96; N, 6.14; Br, 8.76; Na. 2.52. The NMR is consistent with the structure. Crystal suitable for x-ray analysis were grown from ethyl acetate.

1. dissolutionWhen the entire solid had dissolved
2. customthe organic phase was collected
3. washthe aqueous phase washed with diethyl ether, 3×50 mL
4. washThe combined organic extracts were washed with 1×50 mL saturated aqueous sodium chloride
5. dry with materialdried with magnesium sulfate
6. filtrationfiltered
7. customevaporated, under reduced pressure, to an oil, 8.8g (0.0171 mole as the free base)
8. dissolutionThe oil was dissolved in acetonitrile
9. additionTo this solution was added sodium bicarbonate, 1.51 g (0.0180 mole)
10. additionA solution of 5-benzyl, 1-tert-butyl 2-bromopentandioate, 8.02 g (0.0180 mole), in acetonitrile, 40 mL, was added dropwise
11. filtrationThe resulting mixture was filtered
12. concentrationthe filtrate concentrated under reduced pressure
13. customto give a clear colorless oil
14. stirring100 mL, with stirring
15. customThe product began crystallizing after a few minutes
16. stirringAfter stirring for ca. 1 hr
17. filtrationthe product was collected by filtration
18. washwashed with fresh ether and vacuum
19. customdried
20. additionconsisted of a mixture of Na-DO3A-tris (tert-butyl ester) bromide
21. customThe solid was recrystallized twice from minimal ethyl acetate, ca.,100 mL ea
22. custom, giving very pure product

ORD record

ord-d98655b17d40407c8a1e8d35a4089342

Source dataset

uspto-grants-2012_06

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08193347B2