Bis(2-chloroethyl)ethylamine → methyl (S)-3-tert-butoxycarbonylamino-2-(4-ethylpiperazin-1-yl)propanoate

HRID 874581

Reaction equation

HRID 874581 reaction equation
Cl.[NH2:2][C@@H:3]([CH2:8][NH:9][C:10]([O:12][C:13]([CH3:16])([CH3:15])[CH3:14])=[O:11])[C:4]([O:6][CH3:7])=[O:5].Cl[CH2:18][CH2:19][N:20]([CH2:23][CH2:24]Cl)[CH2:21][CH3:22]>C(N(CC)C(C)C)(C)C>[C:13]([O:12][C:10]([NH:9][CH2:8][C@H:3]([N:2]1[CH2:22][CH2:21][N:20]([CH2:23][CH3:24])[CH2:19][CH2:18]1)[C:4]([O:6][CH3:7])=[O:5])=[O:11])([CH3:16])([CH3:15])[CH3:14]

Participants

4

Reactant 2

HCID 10848Bis(2-chloroethyl)ethylamineHCID 18334328methyl (2S)-2-amino-3-{[(tert-butoxy)carbonyl]amino}propanoate hydrochloride

Product 1

HCID 86667916methyl (S)-3-tert-butoxycarbonylamino-2-(4-ethylpiperazin-1-yl)propanoateYield 40.4%

Reagents, catalysts & solvents 1

HCID 81531DiisopropylethylamineSolvent

Procedure

A solution of 5.0 g (19.6 mmol) of commercial methyl (S)-2-amino-3-tert-butoxycarbonylaminopropanoate hydrochloride and 3.3 g (19.6 mmol) of bis(2-chloroethyl)ethylamine in 50 ml of N,N-diisopropylethylamine is heated at 127° C. for 5 h. After evaporation of a maximum amount of diisopropylethylamine, the reaction medium is diluted with ethyl acetate and washed with an aqueous solution of sodium hydroxide having a concentration of 1N. The organic phase obtained is then washed with water, dried over magnesium sulfate, filtered and concentrated under vacuum. The crude product obtained is purified by chromatography on silica gel, elution being carried out with a 30/70 heptane/ethyl acetate mixture. 2.5 g (40%) of methyl (S)-3-tert-butoxycarbonylamino-2-(4-ethylpiperazin-1-yl)propanoate are obtained in the form of an oil.

Workup

  1. customAfter evaporation of a maximum amount of diisopropylethylamine
  2. additionthe reaction medium is diluted with ethyl acetate
  3. washwashed with an aqueous solution of sodium hydroxide having a concentration of 1N
  4. customThe organic phase obtained
  5. washis then washed with water
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. customThe crude product obtained
  10. customis purified by chromatography on silica gel, elution

Sources & evidence

ORD record
ord-38cfb5e90a2341bab8cb438e7d52f29b
Source dataset
uspto-grants-2015_03
Patent number
US08980897B2

Linked notes

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