Tetrahydrofuran → [4-(2-Hydroxy-2-p-tolyl-ethyl)-pyridin-2-yl]-carbamic acid tert-butyl ester

HRID 1023425

Reaktionsgleichung

Reaktionsgleichung von HRID 1023425
[C:1]([O:5][C:6](=[O:15])[NH:7][C:8]1[CH:13]=[C:12]([CH3:14])[CH:11]=[CH:10][N:9]=1)([CH3:4])([CH3:3])[CH3:2].[Li][CH2:17][CH2:18][CH2:19][CH3:20].CCCCCC.[NH4+].[Cl-].[CH2:29]1[CH2:33][O:32][CH2:31][CH2:30]1>O.CCOC(C)=O>[C:1]([O:5][C:6](=[O:15])[NH:7][C:8]1[CH:13]=[C:12]([CH2:14][CH:31]([OH:32])[C:30]2[CH:29]=[CH:33][C:19]([CH3:20])=[CH:18][CH:17]=2)[CH:11]=[CH:10][N:9]=1)([CH3:4])([CH3:3])[CH3:2]

Komponenten

8

Edukt 5

HCID 8028TetrahydrofuranHCID 8058HexaneHCID 25517Ammonium ChlorideHCID 11063648tert-butyl N-(4-methylpyridin-2-yl)carbamateHCID 178418339Butyllithium

Produkt 1

HCID 69082872[4-(2-Hydroxy-2-p-tolyl-ethyl)-pyridin-2-yl]-carbamic acid tert-butyl ester

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittel

Versuchsvorschrift

The solution of (4-methyl-pyridin-2-yl)-carbamic acid tert-butyl ester (200 mg, 0.96 mmol) in dry THF (10 mL) is cooled to −78° C. The 1.6 M n-BuLi in hexane solution (3.0 mL, 4.8 mmol) is added dropwise at −78° C. Then the cooling bath is removed and the mixture is stirred at room temperature for 15 min. The reaction mixture is cooled down to −78° C. again and 4-methylbenzylaldehyde (231 mg, 1.9 mmol) is added. The mixture is stirred for another 30 min at −78° C. and saturated NH4Cl aquaous solution (25 mL) is added. The reaction mixture is then warmed up to room temperature and EtOAc (30 mL) is added along with water (30 mL). The resulting mixture is stirred for 10 min and the aqueous layer is separated and extracted with EtOAc (3×35 ml). The combined organic layers are washed with brine, dried over anhydrous sodium sulfate and concentrated. The crude is purified by silica flash column chromatography eluting with EtOAc in Heptane (gradient from 0% to 60%) to give 80 mg of the desired product.

Aufarbeitung

  1. customThen the cooling bath is removed
  2. temperatureThe reaction mixture is cooled down to −78° C. again
  3. stirringThe mixture is stirred for another 30 min at −78° C.
  4. temperatureThe reaction mixture is then warmed up to room temperature
  5. stirringThe resulting mixture is stirred for 10 min
  6. customthe aqueous layer is separated
  7. extractionextracted with EtOAc (3×35 ml)
  8. washThe combined organic layers are washed with brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. concentrationconcentrated
  11. customThe crude is purified by silica flash column chromatography
  12. washeluting with EtOAc in Heptane (gradient from 0% to 60%)

Quellen und Nachweise

ORD-Eintrag
ord-d4ad2536a1434885b4daae1ac8e9d73e
Quelldatensatz
uspto-grants-2014_05
Patentnummer
US08722709B2

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