N-(tert-butoxycarbonyl)glycine → (3S)-1-Cbz-3-{cyclohexyl[(N-BOC)aminoacetyl]amino}pyrrolidine

HRID 1670014Notes

Reaction equation

HRID 1670014 reaction equation
[C:1]([N:11]1[CH2:15][CH2:14][C@H:13]([NH:16][CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)[CH2:12]1)([O:3][CH2:4][C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][CH:6]=1)=[O:2].CCN(C(C)C)C(C)C.CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[NH:56]([C:61]([O:63][C:64]([CH3:67])([CH3:66])[CH3:65])=[O:62])[CH2:57][C:58](O)=[O:59]>CN(C=O)C>[C:1]([N:11]1[CH2:15][CH2:14][C@H:13]([N:16]([CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][CH2:18]2)[C:58](=[O:59])[CH2:57][NH:56][C:61]([O:63][C:64]([CH3:66])([CH3:65])[CH3:67])=[O:62])[CH2:12]1)([O:3][CH2:4][C:5]1[CH:6]=[CH:7][CH:8]=[CH:9][CH:10]=1)=[O:2]

Participants

6

Reactant 4

HCID 78288N-(tert-butoxycarbonyl)glycineHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 67343263HCID 67343263, compound2×

Product 1

HCID 67343791(3S)-1-Cbz-3-{cyclohexyl[(N-BOC)aminoacetyl]amino}pyrrolidineYield 100.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (3S)-1-Cbz-3-{cyclohexylamino}pyrrolidine (3.0 g, 10.0 mmol), prepared in Intermediate 2, in DMF (30 mL) were added DIPEA (3.50 mL, 20.0 mmol), HBTU (4.88 g, 13 mmol), BOC-Gly (1.92 g, 11 mmol). After the mixture was stirred at rt for 4 h, the solvent was removed in vacuo, and the residue was diluted with an aqueous NaHCO3. The organic material was extracted with EtOAc, and the organic extracts were washed with 1N HCl, dried over MgSO4, concentrated in vacuo. The residue was purified by column chomatography (EtOAc/Hex=1/3) to give the title compound (4.63 g, 92.0%).

Workup

  1. customthe solvent was removed in vacuo
  2. additionthe residue was diluted with an aqueous NaHCO3
  3. extractionThe organic material was extracted with EtOAc
  4. washthe organic extracts were washed with 1N HCl
  5. dry with materialdried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by column chomatography (EtOAc/Hex=1/3)

Sources & evidence

ORD record
ord-996032b83d3546c9a50819abcdee531b
Source dataset
uspto-grants-2011_08
Patent number
US07989634B2

Reaction notes

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