Sodium Hydroxide → tert-Butyl 4-((S)-3-(benzyloxycarbonylamino)-2-oxopyrrolidin-1-yl)-3,3-dimethylpiperidine-1-carboxylate

HRID 408022Notes

Reaction equation

HRID 408022 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C@@H:12]([CH2:16][CH2:17][NH:18][CH:19]1[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:31])([CH3:30])[CH3:29])=[O:26])[CH2:21][C:20]1([CH3:33])[CH3:32])[C:13]([OH:15])=O)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.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.[OH-].[Na+]>CN(C=O)C.CCOC(C)=O>[CH2:1]([O:8][C:9]([NH:11][C@H:12]1[CH2:16][CH2:17][N:18]([CH:19]2[CH2:24][CH2:23][N:22]([C:25]([O:27][C:28]([CH3:30])([CH3:29])[CH3:31])=[O:26])[CH2:21][C:20]2([CH3:33])[CH3:32])[C:13]1=[O:15])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 14798Sodium HydroxideHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 86688122(2S)-2-(benzyloxycarbonylamino)-4-(1-(tert-butoxycarbonyl)-3,3-dimethylpiperidin-4-ylamino)butanoic acid

Product 1

HCID 67469782tert-Butyl 4-((S)-3-(benzyloxycarbonylamino)-2-oxopyrrolidin-1-yl)-3,3-dimethylpiperidine-1-carboxylateYield 23.3%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (25)-2-(benzyloxycarbonylamino)-4-(1-(tert-butoxycarbonyl)-3,3-dimethylpiperidin-4-ylamino)butanoic acid (3.59 g, 7.74 mmol) in DMF (20 mL) was added DIEA (4.1 mL, 23 mmol) and HBTU (3.5 g, 9.3 mmol). The mixture stirred at ambient temperature overnight. The mixture was poured into 1 N NaOH solution and extracted into ethyl acetate. The organic layer was washed with 1 N HCl solution and brine, dried over MgSO4, filtered and concentrated under vacuum. Flash chromatography (7:3 EtOAc:hexanes) gave tert-butyl 4-((S)-3-(benzyloxycarbonylamino)-2-oxopyrrolidin-1-yl)-3,3-dimethylpiperidine-1-carboxylate (0.81 g, 1.8 mmol, 23%) as a white solid.

Workup

  1. extractionextracted into ethyl acetate
  2. washThe organic layer was washed with 1 N HCl solution and brine
  3. dry with materialdried over MgSO4
  4. filtrationfiltered
  5. concentrationconcentrated under vacuum

Sources & evidence

ORD record
ord-bea64ec26f9e4557a5107b5291be6888
Source dataset
uspto-grants-2014_06
Patent number
US08754226B2

Reaction notes

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