N-Benzylnormechlorethamine → HCID 71115295, compound

HRID 874576Notes

Reaction equation

HRID 874576 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].[CH2:17]([N:24]([CH2:28][CH2:29]Cl)[CH2:25][CH2:26]Cl)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1>C(N(CC)C(C)C)(C)C>[CH2:17]([N:24]1[CH2:28][CH2:29][N: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])[CH2:26][CH2:25]1)[C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1

Participants

4

Reactant 2

HCID 5928N-BenzylnormechlorethamineHCID 18334328methyl (2S)-2-amino-3-{[(tert-butoxy)carbonyl]amino}propanoate hydrochloride

Product 1

HCID 71115295HCID 71115295, compoundYield 102.5%

Reagents, catalysts & solvents 1

HCID 81531DiisopropylethylamineSolvent

Procedure

A solution of 5.9 g (23 mmol) of commercial methyl (S)-2-amino-3-tert-butoxycarbonylaminopropanoate hydrochloride and of 9.6 g (23 mmol) of benzylbis(2-chloroethyl)amine in 50 ml of N,N-diisopropylethylamine is heated at 127° C. for 3 h 30. After evaporation of the N,N-diisopropylethylamine, the reaction medium is hydrolyzed and then extracted with ethyl acetate. The organic phase is washed with an aqueous solution of sodium hydroxide having a concentration of 1N, and with water, and then 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 50/50 heptane/ethyl acetate mixture. 8.9 g (64%) of methyl (S)-2-(4-benzylpiperazin-1-yl)-3-tert-butoxycarbonylaminopropanoate are obtained in the form of a yellow oil.

Workup

  1. customAfter evaporation of the N,N-diisopropylethylamine
  2. extractionextracted with ethyl acetate
  3. washThe organic phase is washed with an aqueous solution of sodium hydroxide having a concentration of 1N
  4. dry with materialwith water, and then dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated under vacuum
  7. customThe crude product obtained
  8. customis purified by chromatography on silica gel, elution

Sources & evidence

ORD record
ord-6c9cb8c937db4bd2a9cc0c04fdb4719c
Source dataset
uspto-grants-2015_03
Patent number
US08980897B2

Reaction notes

Loading…