反应详情

To a flask containing 6-bromo-4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline (2.0 g, 4.64 mmol, Intermediate 12: step d) was added THF (65 mL) and the solution was cooled to −78° C. n-BuLi (2.5 M in hexanes, 2.1 mL, 5.25 mmol) was added dropwise producing a dark reddish-brown mixture. After 2 minutes, a THF solution of 3,5-dimethylisoxazole-4-carbaldehyde (700 mg, 5.63 mmol in 2 mL THF) was introduced. The reaction mixture immediately became a homogeneous yellow solution. After 25 minutes the mixture was quenched with aqueous NH4Cl solution and the aqueous portion was extracted with EtOAc (3×50 mL). The combined organics were washed with brine, dried over MgSO4, filtered and concentrated to dryness. Chromatography on silica gel (100% DCM increasing to 20% CH3CN/DCM) provided the titled compound an off white amorphous solid.

1. additionwas added dropwise
2. customproducing a dark reddish-brown mixture
3. customAfter 25 minutes the mixture was quenched with aqueous NH4Cl solution
4. extractionthe aqueous portion was extracted with EtOAc (3×50 mL)
5. washThe combined organics were washed with brine
6. dry with materialdried over MgSO4
7. filtrationfiltered
8. concentrationconcentrated to dryness