methyl (2S)-2-amino-3-{[(tert-butoxy)carbonyl]amino}propanoate hydrochloride → methyl (S)-3-tert-butoxycarbonylamino-2-[4-(4-trifluoromethylbenzyl)piperazin-1-yl]propanoate

HRID 472141Notes

Reaction equation

HRID 472141 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]([CH2:32][CH2:33]Cl)[CH2:21][C:22]1[CH:27]=[CH:26][C:25]([C:28]([F:31])([F:30])[F:29])=[CH:24][CH:23]=1>C(N(CC)C(C)C)(C)C>[C:13]([O:12][C:10]([NH:9][CH2:8][C@H:3]([N:2]1[CH2:18][CH2:19][N:20]([CH2:21][C:22]2[CH:23]=[CH:24][C:25]([C:28]([F:29])([F:31])[F:30])=[CH:26][CH:27]=2)[CH2:32][CH2:33]1)[C:4]([O:6][CH3:7])=[O:5])=[O:11])([CH3:16])([CH3:15])[CH3:14]

Participants

4

Reactant 2

HCID 18334328methyl (2S)-2-amino-3-{[(tert-butoxy)carbonyl]amino}propanoate hydrochlorideHCID 66870563Bis(2-chloroethyl)(4-trifluoromethylbenzyl)amine

Product 1

HCID 86675026methyl (S)-3-tert-butoxycarbonylamino-2-[4-(4-trifluoromethylbenzyl)piperazin-1-yl]propanoateYield 55%

Reagents, catalysts & solvents 1

HCID 81531DiisopropylethylamineSolvent

Procedure

A solution of 4.2 g (16.5 mmol) of methyl (S)-2-amino-3-tert-butoxycarbonylaminopropanoate hydrochloride and 4.95 g (16.5 mmol) of bis(2-chloroethyl)(4-trifluoromethylbenzyl)amine in 25 ml of N,N-diisopropylethylamine is heated at 127° C. for 6 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 washed with water, dried over magnesium sulfate, filtered and concentrated under vacuum. The crude residue is purified by chromatography on silica gel, elution being carried out with a 60/40 heptane/ethyl acetate mixture. 4.0 g (55%) of methyl (S)-3-tert-butoxycarbonylamino-2-[4-(4-trifluoromethylbenzyl)piperazin-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 washed with water
  6. dry with materialdried over magnesium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated under vacuum
  9. customThe crude residue is purified by chromatography on silica gel, elution

Sources & evidence

ORD record
ord-e8039efc7f844f39ab20553010ea497b
Source dataset
uspto-grants-2014_01
Patent number
US08633196B2

Reaction notes

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