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

Tert-butyl 4-[(2R)-3-benzyloxycarbonylamino-2-hydroxy-propyl]piperazine-1-carboxylate 20c (1.80 g, 4.80 mmol) was dissolved in 30 mL of dichloromethane followed by the addition of 20 mL of a solution of hydrogen chloride in dioxane. The reaction solution was stirred for 0.5 hours. The reaction solution was concentrated under reduced pressure, added with 30 mL of water and 30 mL of acetonitrile, formaldehyde (288 mg, 9.6 mmol) and dropwise with 0.1 mL of acetic acid. The resulting solution was stirred for 0.5 hours followed by the addition of sodium triacetoxyborohydride (3.05 g, 14.40 mmol). The reaction solution was stirred for 12 hours, added dropwise with saturated sodium carbonate solution to adjust pH to 10 and extracted with ethyl acetate (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-[(2R)-2-hydroxy-3-(4-methylpiperazin-1-yl)propyl]carbamate 20d (830 mg, yield: 56.0%) as a yellow oil.

1. concentrationThe reaction solution was concentrated under reduced pressure
2. stirringThe resulting solution was stirred for 0.5 hours
3. stirringThe reaction solution was stirred for 12 hours
4. extractionextracted with ethyl acetate (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 record

ord-d68d9c76b358468e9bb5d7811d7c7d4d

Source dataset

uspto-grants-2014_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08691822B2