Hydrochloric Acid → 1-Benzyl-3(S)-(2'-methylbenzyl)-piperazine-2,5-dione

HRID 1423078Notes

Reaction equation

HRID 1423078 reaction equation
[C:1]([NH:8][C@H:9]([C:18]([OH:20])=O)[CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=1[CH3:17])([O:3]C(C)(C)C)=O.C1C=CC2N(O)N=NC=2C=1.C(N(C(C)C)CC)(C)C.C(OC(=O)[CH2:44][NH:45][CH2:46][C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.Cl>CN(C=O)C.CCOC(C)=O>[CH2:46]([N:45]1[CH2:44][C:1](=[O:3])[NH:8][C@@H:9]([CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[CH3:17])[C:18]1=[O:20])[C:47]1[CH:52]=[CH:51][CH:50]=[CH:49][CH:48]=1

Participants

9

Reactant 6

HCID 313Hydrochloric AcidHCID 757711-HydroxybenzotriazoleHCID 80908N-Benzylglycine ethyl esterHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 2761468Boc-L-2-Methylphenylalanine

Product 1

HCID 668249411-Benzyl-3(S)-(2'-methylbenzyl)-piperazine-2,5-dioneYield 139.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

A solution of Boc-2-methyl-L-phenylalanine (2.79 g, 10 mmol) in DMF (25 mL) was treated sequentially with HOBt (2.03 g, 15 mmol), diisopropylethylamine (4.35 mL, 25 mmol), N-benzylglycine ethyl ester (2.03 mL, 11 mmol), and HBTU (5.69 g, 15 mmol). The resulting solution was allowed to stir for 16 h after which time the mixture was poured onto a mixture of a 1 N aqueous HCl (50 mL) solution and EtOAc (50 mL). The organic portion was separated and further extracted with a saturated aqueous NaHCO3 solution (50 mL) follow by brine (50 mL). The organic phase was dried over MgSO4, filtered and evaporated to an oil, which was purified by silica gel flash chromatography with 20% then 30% EtOAc/hexanes as eluant to afford titled compound as a solid (4.31 g, 95%). LC/MS (Method A) 7.43 min, [M+1]+ 455.

Workup

  1. customThe organic portion was separated
  2. extractionfurther extracted with a saturated aqueous NaHCO3 solution (50 mL)
  3. dry with materialThe organic phase was dried over MgSO4
  4. filtrationfiltered
  5. customevaporated to an oil, which
  6. customwas purified by silica gel flash chromatography with 20%

Sources & evidence

ORD record
ord-bfb2b5135f51465ab44abbdc0ce8a51b
Source dataset
uspto-grants-2015_01
Patent number
US08927546B2

Reaction notes

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