Ammonia → HCID 15408476, compound

A solution of N,N'-bis(2-mercapto-2-methylpropyl)ethylenediamine (11.23 g, 47.5 mmol; see, DiZio et al., 1991, Bioconjugate Chem 2: 353 and Corbin et al., 1976, J. Org. Chem. 41: 489) in methanol (500 mL) was cooled in ice/water bath and then saturated with gaseous ammonia over 45 min. To this was added 4-methoxybenzyl chloride (17.0 mL, 125 mmol, 264 mol %). The reaction was allowed to warm to room temperature overnight with stirring under argon. The solution was concentrated to a paste and then partitioned between diethyl ether (150 mL) and 0.5M KOH (200 mL). The aqueous layer was further extracted with diethyl ether (2×50 mL). The combined organic layers were washed with NaCl solution and concentrated to a clear colorless oil. The oil dissolved in diethyl ether (200 mL) and then acidified with 4.0M HCI in dioxane until no further precipitation was seen. The white precipitate was collected by filtration and washed with diethyl ether. The white solid was recrystallized from hot water at a pH of ~2. The product was collected by filtration to afford 29.94 g as a mix of mono- and di- HCl salts. The HCl salts were partitioned between 1M KOH (100 mL) and ethyl acetate (100 mL). The aqueous was extracted with ethyl acetate (2×30 mL) and the combined organic layers were washed with NaCl solution, dried with Na2 SO4 and concentrated to give pure product as the free base as a light yellow oil (18.53 g, 82% yield). Nuclear magnetic resonance characterization experiments yielded the following molecular signature:

1. concentrationThe solution was concentrated to a paste
2. custompartitioned between diethyl ether (150 mL) and 0.5M KOH (200 mL)
3. extractionThe aqueous layer was further extracted with diethyl ether (2×50 mL)
4. washThe combined organic layers were washed with NaCl solution
5. concentrationconcentrated to a clear colorless oil
6. dissolutionThe oil dissolved in diethyl ether (200 mL)
7. customacidified with 4.0M HCI in dioxane until no further precipitation
8. filtrationThe white precipitate was collected by filtration
9. washwashed with diethyl ether
10. customThe white solid was recrystallized from hot water at a pH of ~2
11. filtrationThe product was collected by filtration
12. customto afford 29.94 g as
13. customThe HCl salts were partitioned between 1M KOH (100 mL) and ethyl acetate (100 mL)
14. extractionThe aqueous was extracted with ethyl acetate (2×30 mL)
15. washthe combined organic layers were washed with NaCl solution
16. customdried with Na2 SO4
17. concentrationconcentrated

ORD record

ord-cbe0e4ab318e4c228f10d6d203eb72da

Source dataset

uspto-grants-1998_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US05849261