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

HRID 416360노트

반응식

HRID 416360 반응식
[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

참가 물질

8

반응물 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

생성물 1

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

시약·촉매·용매 3

HCID 962Water용매HCID 8028Tetrahydrofuran용매HCID 8857Ethyl Acetate용매

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-5c328452b8bf4ed39f063a289ea7288e
출처 데이터셋
uspto-grants-2012_01
특허 번호
US08088793B2

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