tert-Butyl piperazine-1-carboxylate → tert-Butyl 4-((1-methyl-1H-imidazol-5-yl)methyl)piperazine-1-carboxylate

HRID 416918

Reaktionsgleichung

Reaktionsgleichung von HRID 416918
[C:1]([N:8]1[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1)([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2].[CH3:14][N:15]1[C:19]([CH:20]=O)=[CH:18][N:17]=[CH:16]1.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+]>ClCCCl>[CH3:14][N:15]1[C:19]([CH2:20][N:11]2[CH2:10][CH2:9][N:8]([C:1]([O:3][C:4]([CH3:7])([CH3:6])[CH3:5])=[O:2])[CH2:13][CH2:12]2)=[CH:18][N:17]=[CH:16]1

Komponenten

5

Edukt 3

HCID 143452tert-Butyl piperazine-1-carboxylateHCID 5735921-methyl-1H-imidazole-5-carbaldehydeHCID 5049666Sodium triacetoxyborohydride

Produkt 1

HCID 57897271tert-Butyl 4-((1-methyl-1H-imidazol-5-yl)methyl)piperazine-1-carboxylateAusbeute 22 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 111,2-DichloroethaneLösungsmittel

Versuchsvorschrift

N-Boc-piperazine (0.930 g, 5.0 mmol, 1.1 eq) was dissolved in 1,2-DCE (14 mL). To this solution, 1-methyl-1H-imidazole-5-carboxaldehyde (0.500 g, 4.54 mmol, 1 eq) was added followed by the portionwise addition of sodium triacetoxyborohydride (1.35 g, 6.36 mmol, 1.4 eq). The mixture was stirred at room temperature for 4 h and was then washed with a saturated aqueous solution of NaHCO3. The organic layer was dried (MgSO4), and the solvent removed in vacuo. The crude mixture was redissolved in 18 mL of DCM and gently stirred overnight in the presence of PS-isocyanate (2 g, loading: 1.58 mmol/g). The mixture was filtered off, and the resin washed with DCM (2×10 mL). The solvent was removed in vacuo and the resulting mixture was purified by column chromatography on a Biotage SP1 system eluting with methanol (2-10%) in dichloromethane to give the title compound (0.280 g, 22%); 1H-NMR (500 MHz, CDCl3): δ 1.45 (s, 9H, C(CH3)3), 2.28-2.40 (m, 4H, piperazine N(CH2)2), 3.38 (m, 4H, piperazine N(CH2)2), 3.44 (s, 2H, NCH2), 3.66 (s, 3H, imidazole Me), 6.87 (s, 1H, imidazole 4-H), 7.40 (s, 1H, imidazole 2-H); GC-MS (Cl, m/z): Rt=4.89 min—281 [(M+H)+, 100%].

Aufarbeitung

  1. washwas then washed with a saturated aqueous solution of NaHCO3
  2. dry with materialThe organic layer was dried (MgSO4)
  3. customthe solvent removed in vacuo
  4. dissolutionThe crude mixture was redissolved in 18 mL of DCM and gently stirred overnight in the presence of PS-isocyanate (2 g, loading: 1.58 mmol/g)
  5. filtrationThe mixture was filtered off
  6. washthe resin washed with DCM (2×10 mL)
  7. customThe solvent was removed in vacuo
  8. customthe resulting mixture was purified by column chromatography on a Biotage SP1 system
  9. washeluting with methanol (2-10%) in dichloromethane

Quellen und Nachweise

ORD-Eintrag
ord-1599976c7b1a445c8a540ce757e12f85
Quelldatensatz
uspto-grants-2012_01
Patentnummer
US08088761B2

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