Reaktionsgleichung
Br[C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][N:3]=1.C[Si](C)(C)[O:11][C:12]1[CH:19]=[CH:18][C:15]([CH:16]=[O:17])=[CH:14][CH:13]=1>C1COCC1>[OH:17][CH:16]([C:2]1[CH:7]=[CH:6][C:5]([CH3:8])=[CH:4][N:3]=1)[C:15]1[CH:18]=[CH:19][C:12]([OH:11])=[CH:13][CH:14]=1Komponenten
Edukt 2
Produkt 1
Reagenzien, Katalysatoren, Lösungsmittel 1
Reaktionsbedingungen
- Temperatur
- -40 °C
Versuchsvorschrift
To a stirred solution of 2-bromo-5-methylpyridine (3.45 g, 20 mmol) in THF (10 mL) was added dropwise 1.6 M solution in hexanes n-BuLi (12 mL, 19.2 mmol) over a 10-min period at −78° C. The mixture was stirred at −78° C. for 2 min before 4-trimethylsilyloxybenzaldehyde (4.2 g, 21.6 mmol) dissolved in THF (10 mL) was added. The mixture was allowed to warm to −40° C. and quenched with water. The pH of the aqueous phase was adjusted to 7 which causes precipitation of 4-[hydroxy-(5-methyl-pyridin-2-yl)-methyl]phenol. This was isolated by filtration to give 1.13 g (27%) of 4-[hydroxy-(5-methyl-pyridin-2-yl)-methyl]phenol as crystals. This intermediate was dissolved in CH2Cl2 (15 mL) and stirred with triethylsilane (4 mL) and TFA (5 mL) for 16 h at 50° C. Evaporation gave 99% of 4-(5-methyl-pyridin-2-ylmethyl)phenol as a hygroscopic solid. This was carbamoylated using general procedure 1 (CH2Cl2 was used as solvent and N-phenyl-N-methyl carbamoyl chlorid) to give 99% of the title product as its crystalline hydrochloride after purification by flash chromatography (Quad flash 12, EtOAc-heptane) and treatment with HCl in Et2O.
Aufarbeitung
- additionwas added
- customquenched with water
- customprecipitation of 4-[hydroxy-(5-methyl-pyridin-2-yl)-methyl]phenol
- customThis was isolated by filtration
Quellen und Nachweise
- ORD-Eintrag
- ord-2acb9c7749bb4933ad3baef289330b4b
- Quelldatensatz
- uspto-grants-2007_10
- Patentnummer
- US07279470B2
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