Hydrochloric Acid → benzyl N-[(2S)-2-hydroxy-3-(4-methylpiperazin-1-yl)propyl]carbamate

Tert-butyl 4-[(2S)-3-benzyloxycarbonylamino-2-hydroxy-propyl]piperazine-1-carboxylate 21a (1.45 g, 3.70 mmol) was dissolved in 30 mL of dichloromethane followed by the addition of 20 mL of a 4 M solution of hydrogen chloride in dioxane. The reaction solution was stirred for 0.5 hours and concentrated under reduced pressure. The residue was added with 40 mL of dichloromethane, formaldehyde (222 mg, 7.40 mmol) and 0.1 mL of acetic acid successively. The resulting solution was stirred for 0.5 hours followed by the addition of sodium triacetoxyborohydride (2.35 g, 11.10 mmol), stirred for another 12 hours. The resulting solution was added with 50 mL of water and extracted with dichloromethane (50 mL×3). The combined organic phase was washed with saturated sodium chloride solution (50 mL×3), then dried over anhydrous magnesium sulfate, filtered and the filtrate was concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography to obtain the title compound benzyl N-[(2S)-2-hydroxy-3-(4-methylpiperazin-1-yl)propyl]carbamate 21b (840 mg, yield: 74.0%) as a yellow oil.

1. concentrationconcentrated under reduced pressure
2. stirringThe resulting solution was stirred for 0.5 hours
3. stirringstirred for another 12 hours
4. extractionextracted with dichloromethane (50 mL×3)
5. washThe combined organic phase was washed with saturated sodium chloride solution (50 mL×3)
6. dry with materialdried over anhydrous magnesium sulfate
7. filtrationfiltered
8. concentrationthe filtrate was concentrated under reduced pressure
9. customThe resulting residue was purified by silica gel column chromatography

ORD-Eintrag

ord-6149c643d7d342da880240d2faec2616

Quelldatensatz

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US08691822B2