N-Benzylnormechlorethamine → HCID 71115295, compound

HRID 472135Notes

Reaction equation

HRID 472135 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-ac7c2500bc92481491fe1ca7edc9dfda
Source dataset
uspto-grants-2014_01
Patent number
US08633196B2

Reaction notes

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