Water → Tert-butyl 4-(((2-chloro-5-iodopyridin-4-yl)amino)methyl)piperidine-1-carboxylate

HRID 384696

Reaktionsgleichung

Reaktionsgleichung von HRID 384696
[H-].[Na+].[Cl:3][C:4]1[CH:9]=[C:8]([NH2:10])[C:7]([I:11])=[CH:6][N:5]=1.Br[CH2:13][CH:14]1[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:26])([CH3:25])[CH3:24])=[O:21])[CH2:16][CH2:15]1.O>CN(C=O)C>[Cl:3][C:4]1[CH:9]=[C:8]([NH:10][CH2:13][CH:14]2[CH2:19][CH2:18][N:17]([C:20]([O:22][C:23]([CH3:24])([CH3:26])[CH3:25])=[O:21])[CH2:16][CH2:15]2)[C:7]([I:11])=[CH:6][N:5]=1

Komponenten

6

Edukt 4

HCID 962WaterHCID 24758Sodium hydride2×HCID 15512811tert-Butyl 4-(bromomethyl)piperidine-1-carboxylateHCID 454803662-Chloro-5-iodopyridin-4-amine

Produkt 1

HCID 59613389Tert-butyl 4-(((2-chloro-5-iodopyridin-4-yl)amino)methyl)piperidine-1-carboxylateAusbeute 46 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel2×

Versuchsvorschrift

NaH (0.098 g, 3.9 mmol) was added to a solution of 2-chloro-5-iodopyridin-4-amine (0.500 g, 1.96 mmol) in DMF (12 mL) and the mixture was stirred for 30 min at r.t. The temperature was then raised to 80° C. and a solution of tert-butyl 4-(bromomethyl)-piperidine-1-carboxylate (1.093 g, 3.93 mmol) in DMF (2 mL) was added. The reaction mixture was stirred at 80° C. for 2 h, then cooled to r.t. NaH (0.050 g, 2.00 mmol) was added and the reaction mixture was heated for 1 h at 80° C. After cooling, water (40 mL) was added and the reaction mixture was partitioned between ethyl acetate and aq. NaHCO3. The organic phase was washed with brine, dried (MgSO4) and concentrated. The crude product was purified by flash silica chromatography, eluting with ethyl acetate and hexane (1/9), to give the title compound as a pink solid (0.405 g, 46%).

Aufarbeitung

  1. temperatureThe temperature was then raised to 80° C.
  2. stirringThe reaction mixture was stirred at 80° C. for 2 h
  3. temperaturecooled to r.t
  4. temperaturethe reaction mixture was heated for 1 h at 80° C
  5. temperatureAfter cooling
  6. customthe reaction mixture was partitioned between ethyl acetate and aq. NaHCO3
  7. washThe organic phase was washed with brine
  8. dry with materialdried (MgSO4)
  9. concentrationconcentrated
  10. customThe crude product was purified by flash silica chromatography
  11. washeluting with ethyl acetate and hexane (1/9)

Quellen und Nachweise

ORD-Eintrag
ord-5d36f32fe1da480b9bdffd7e3691fc9a
Quelldatensatz
uspto-grants-2013_02
Patentnummer
US08367658B2

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