Water → methyl (R)-3-tert-butoxycarbonylamino-2-(4-methanesulphonyl-piperazin-1-yl)propanoate

HRID 517500Notes

Reaction equation

HRID 517500 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]([CH2:25][CH2:26]Cl)[S:21]([CH3:24])(=[O:23])=[O:22].O>C(N(CC)C(C)C)(C)C>[C:13]([O:12][C:10]([NH:9][CH2:8][C@@H:3]([N:2]1[CH2:26][CH2:25][N:20]([S:21]([CH3:24])(=[O:23])=[O:22])[CH2:19][CH2:18]1)[C:4]([O:6][CH3:7])=[O:5])=[O:11])([CH3:16])([CH3:15])[CH3:14]

Participants

5

Reactant 3

HCID 962WaterHCID 245092n,n-Bis(2-chloroethyl)methanesulfonamideHCID 51358429(R)-Methyl 2-amino-3-((tert-butoxycarbonyl)amino)propanoate hydrochloride

Product 1

HCID 67056910methyl (R)-3-tert-butoxycarbonylamino-2-(4-methanesulphonyl-piperazin-1-yl)propanoateYield 44.1%

Reagents, catalysts & solvents 1

HCID 81531DiisopropylethylamineSolvent

Procedure

A solution of 6 g (23.6 mmol) of methyl (R)-2-amino-3-tert-butoxycarbonylaminopropanoate hydrochloride and 5.2 g (23.6 mmol) of N,N-bis(2-chloroethyl)methanesulphonamide in 80 ml of N,N-diisopropylethylamine is heated at 125° C. with vigorous stirring for 18 h. After addition of water, the product is extracted with ethyl acetate. The organic phases are combined, washed with water, dried over magnesium sulphate, filtered and concentrated under vacuum. The crude product obtained is purified by chromatography over silica gel eluted with a 5/5 heptane/ethyl acetate mixture. 3.8 g (44%) of methyl (R)-3-tert-butoxycarbonylamino-2-(4-methanesulphonylpiperazin-1-yl)propanoate are obtained in the form of a white solid.

Workup

  1. extractionthe product is extracted with ethyl acetate
  2. washwashed with water
  3. dry with materialdried over magnesium sulphate
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum
  6. customThe crude product obtained
  7. customis purified by chromatography over silica gel
  8. washeluted with a 5/5 heptane/ethyl acetate mixture

Sources & evidence

ORD record
ord-9bb9523c700248b9a01547df2c48ab39
Source dataset
uspto-grants-2015_08
Patent number
US09115102B2

Reaction notes

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