3,5-Dimethyl-4-Isoxazolecarbaldehyde → (4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(3,5-dimethylisoxazol-4-yl)methanol

HRID 926546Notes

Reaction equation

HRID 926546 reaction equation
[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH:12]([C:14]3[C:15]([CH3:21])=[N:16]C(C)=[CH:18][CH:19]=3)[OH:13])[CH:10]=2)[N:5]=[C:4]([O:22][CH3:23])[C:3]=1[CH2:24][C:25]1[CH:30]=[CH:29][C:28]([C:31]([F:34])([F:33])[F:32])=[CH:27][CH:26]=1.[Li]CCCC.CC1C(C=O)=C(C)[O:43]N=1>C1COCC1>[Cl:1][C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[C:9]([CH:12]([C:14]3[C:15]([CH3:21])=[N:16][O:43][C:19]=3[CH3:18])[OH:13])[CH:10]=2)[N:5]=[C:4]([O:22][CH3:23])[C:3]=1[CH2:24][C:25]1[CH:26]=[CH:27][C:28]([C:31]([F:34])([F:32])[F:33])=[CH:29][CH:30]=1

Participants

5

Reactant 3

HCID 2895763,5-Dimethyl-4-IsoxazolecarbaldehydeHCID 86715629(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(2,6-dimethylpyridin-3-yl)methanol2×HCID 178418339Butyllithium

Product 1

HCID 118005804(4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(3,5-dimethylisoxazol-4-yl)methanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

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.

Workup

  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

Sources & evidence

ORD record
ord-276a83fd897843fa9488fc3deac693cb
Source dataset
uspto-grants-2016_03
Patent number
US09284308B2

Reaction notes

Loading…