Reaktion #335622

Reaktionsgleichung

methyl 4'-bromomethylbiphenyl-2-carboxylate

2-butyl-4-chloro-5-(t-butyldimethylsilyloxymethyl)-1H-imidazole

NaN(TMS)2

→

4'-[[2-Butyl-4-chloro-5-(t-butyldimethylsilyloxymethyl)-1H-imidazol-1-yl]methyl][1,1'-biphenyl-2-yl]carboxylic acid methyl ester

Lösungsmittel

THF

THF

brine

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigethe organic layer was collected
2. 2
   Trocknendried over MgSO4
3. 3
   Sonstigeevaporated under reduced pressure
4. 4
   SonstigeThe residue was purified by flash chromatography (EtOAc, silica)
5. 5
   Sonstigeto separate the two regioisomeric alkylation products

Vorschrift

A solution of methyl 4'-bromomethylbiphenyl-2-carboxylate (2.05 g) in dry THF (10 mL) was added dropwise to a solution of 2-butyl-4-chloro-5-(t-butyldimethylsilyloxymethyl)-1H-imidazole (2.03 g) and NaN(TMS)2 (1.48 g) in dry THF (20 mL) at 0° C. and the reaction mixture was stirred at room temperature overnight. It was diluted with brine and the organic layer was collected, dried over MgSO4, and evaporated under reduced pressure. The residue was purified by flash chromatography (EtOAc, silica) to separate the two regioisomeric alkylation products. The major isomer, 4'-[[2-butyl-4 chloro-5-(t-butyldimethylsilyloxymethyl) 1H-imidazol-1-yl]methyl][1,1'-biphenyl-2-yl]carboxylic acid methyl ester (1.4 g) was used in the next step and the regiochemistry of this alkylation product was proven by NOE experiments at the stage of the hydrazide.

Quelle