Lithium Hydroxide → (S)-tert-butyl 4-(4-(benzyloxycarbonylamino)-5-(tert-butyldimethylsilyloxy)pentanoyl)piperazine-1-carboxylate

HRID 416360Notes

Reaction equation

HRID 416360 reaction equation
[Si:1]([O:8][CH2:9][C@@H:10]1[CH2:14][CH2:13][C:12](=[O:15])[N:11]1[C:16]([O:18][CH2:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)=[O:17])([C:4]([CH3:7])([CH3:6])[CH3:5])([CH3:3])[CH3:2].[Li+].[OH-].CN(C(ON1N=NC2C=CC=CC1=2)=[N+](C)C)C.F[P-](F)(F)(F)(F)F.[C:52]([N:59]1[CH2:64][CH2:63][NH:62][CH2:61][CH2:60]1)([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53]>C1COCC1.O.CCOC(C)=O>[CH2:19]([O:18][C:16]([NH:11][C@H:10]([CH2:9][O:8][Si:1]([C:4]([CH3:7])([CH3:5])[CH3:6])([CH3:3])[CH3:2])[CH2:14][CH2:13][C:12]([N:62]1[CH2:61][CH2:60][N:59]([C:52]([O:54][C:55]([CH3:58])([CH3:57])[CH3:56])=[O:53])[CH2:64][CH2:63]1)=[O:15])=[O:17])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1

Participants

8

Reactant 4

HCID 3939Lithium HydroxideHCID 143452tert-Butyl piperazine-1-carboxylateHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 12078685(S)-benzyl 2-((tert-butyldimethylsilyloxy)methyl)-5-oxopyrrolidine-1-carboxylate

Product 1

HCID 57948091(S)-tert-butyl 4-(4-(benzyloxycarbonylamino)-5-(tert-butyldimethylsilyloxy)pentanoyl)piperazine-1-carboxylateYield 56.6%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (S)-benzyl 2-((tert-butyldimethylsilyloxy)methyl)-5-oxopyrrolidine-1-carboxylate (39 g, 0.107 mol) in THF (214 mL) was added LiOH (2 N, 107.4 mL). The reaction mixture was stirred at RT overnight, concentrated to dryness, and dissolved in DMF (100 mL). To the resulting solution were added HBTU (48.9 g, 0.13 mmol) and Boc-piperazine (24 g, 0.13 mol). The reaction mixture was stirred at RT for 1 h and diluted with water (200 mL) and EtOAc (500 mL). The organic layer was washed with water, dried over Na2SO4, filtered and concentrated. The residue was purified on silica gel column using a mixture of EtOAc and hexanes to give (S)-tert-butyl 4-(4-(benzyloxycarbonylamino)-5-(tert-butyldimethylsilyloxy)pentanoyl)piperazine-1-carboxylate (33.3 g, 56.5%). LRMS (M+H) m/z 550.3.

Workup

  1. concentrationconcentrated to dryness
  2. dissolutiondissolved in DMF (100 mL)
  3. stirringThe reaction mixture was stirred at RT for 1 h
  4. washThe organic layer was washed with water
  5. dry with materialdried over Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe residue was purified on silica gel column
  9. additiona mixture of EtOAc and hexanes

Sources & evidence

ORD record
ord-5c328452b8bf4ed39f063a289ea7288e
Source dataset
uspto-grants-2012_01
Patent number
US08088793B2

Reaction notes

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