2,4-Dimethyl-oxazole-5-carbaldehyde → (4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(2,4-dimethyloxazol-5-yl)methanol

Temperatur

-70 °C

To a 50 mL flask containing 6-bromo-4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline (1.5 g, 3.48 mmol, Intermediate 47: step d) was added THF (65 mL) at room temperature which resulted in a colorless homogeneous mixture. The solution was cooled to −70° C. which remained homogeneous and then n-butyllithium (2.5 M in hexanes, 1.62 mL, 4.04 mmol) was added drop wise. The color of the solution became a dark opaque reddish-brown color. After 2 minutes, 2,4-dimethyloxazole-5-carbaldehyde (520 mg, 4.16 mmol, in 3 mL THF) was introduced and the color of the mixture went from an opaque dark brown to a light yellow homogeneous color within about 1 minute. After 25 minutes the mixture was quenched with aqueous NH4Cl. The reaction was diluted further with water and extracted with EtOAc (5×40 mL). The combined organics were washed with brine, dried over MgSO4, filtered and concentrated to give a light yellowish foam. The crude material was chromatographed on silica gel (10% CH3CN-DCM grading to 30% CH3CN containing 1% MeOH) to provide the title compound as a white amorphous solid.

1. customresulted in a colorless homogeneous mixture
2. customwithin about 1 minute
3. customAfter 25 minutes the mixture was quenched with aqueous NH4Cl
4. additionThe reaction was diluted further with water
5. extractionextracted with EtOAc (5×40 mL)
6. washThe combined organics were washed with brine
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated
10. customto give a light yellowish foam
11. customThe crude material was chromatographed on silica gel (10% CH3CN-DCM grading to 30% CH3CN containing 1% MeOH)

ORD-Eintrag

ord-12eb47c0b5a044c8aba5b997cd884df9

Quelldatensatz

uspto-grants-2016_03

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US09290476B2