Reaktion #2192211

Reaktionsgleichung

Intermediate 221.1

2-chloro-4-ethyl-1-fluorobenzene

PMDTA

BuLi

Intermediate 175.1

4-bromo-1-trityl-1H-imidazole-2-carbaldehyde

→

Intermediate 221.2

(4-bromo-1-trityl-1H-imidazol-2-yl)(3-chloro-5-ethyl-2-fluorophenyl)methanol

Lösungsmittel

THF

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigerecooled to −70° C.
2. 2
   TemperaturThe mixture was slowly warmed to −20° C. over 1 h
3. 3
   SonstigeThe reaction was quenched with sat. NH4Cl
4. 4
   workup.ADDITIONwas diluted with EtOAc
5. 5
   WaschenThe organic phase was washed with H2O (2×) and brine
6. 6
   Trocknendried (Na2SO4)
7. 7
   Einengenconcentrated
8. 8
   SonstigeThe crude product was purified by flash chromatography (0 to 40% EtOAc/hexanes gradient)

Vorschrift

To a solution of Intermediate 221.1 (100 mg, 0.631 mmol) and PMDTA (0.15 mL) in 5 mL THF at −70° C., was added BuLi (1.4 M in hexanes, 0.473 mL, 0.662 mmol). The mixture was stirred with warming to −40° C. over 30 min, recooled to −70° C., then a solution of Intermediate 175.1 (263 mg, 0.631 mmol) in 2 mL THF was added. The mixture was slowly warmed to −20° C. over 1 h. The reaction was quenched with sat. NH4Cl, then was diluted with EtOAc. The organic phase was washed with H2O (2×) and brine, dried (Na2SO4) and concentrated. The crude product was purified by flash chromatography (0 to 40% EtOAc/hexanes gradient) to afford 312 g of Intermediate 221.2 as a colorless solid. LCMS (50 to 100% B, 4 min gradient, A=95% H2O/5% CH3CN/0.1% TFA, B=5% H2O/95% CH3CN/0.1% TFA) RT=5.45 min, 575.28 (M+H)+.

Quelle