3-Methyl-1,2-oxazole-5-carbaldehyde → (2,4-Dichloro-3-phenylquinolin-6-yl)(3-methylisoxazol-5-yl)methanol

HRID 526829Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([Cl:12])[C:6]([C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[C:5]2[Cl:19].[CH3:20][C:21]1[CH:25]=[C:24]([CH:26]=[O:27])[O:23][N:22]=1.[Li]CCCC>C1COCC1>[Cl:12][C:7]1[C:6]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)=[C:5]([Cl:19])[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([CH:26]([C:24]3[O:23][N:22]=[C:21]([CH3:20])[CH:25]=3)[OH:27])[CH:3]=2)[N:8]=1

Participants

Conditions

Temperature: -78 °C

Procedure

To a mixture of 6-bromo-2,4-dichloro-3-phenylquinoline (363 mg, 1.03 mmol, Intermediate 1: step c) and 3-methylisoxazole-5-carbaldehyde (149 mg, 1.34 mmol) in THF (5 mL) at −78° C. was added n-BuLi (1.6 M in hexane, 0.707 mL, 1.13 mmol) dropwise. The mixture was stirred at −78° C. for 30 minutes, then moved to an ice bath and stirred for 30 minutes. The reaction was quenched by addition of saturated aqueous NH4Cl and then diluted with water. The mixture was extracted three times with EtOAc. The organic phase was dried (Na2SO4), filtered, and concentrated to afford the crude title compound which was used without further purification in the next reaction.

Workup

custommoved to an ice bath
stirringstirred for 30 minutes
customThe reaction was quenched by addition of saturated aqueous NH4Cl
additiondiluted with water
extractionThe mixture was extracted three times with EtOAc
dry with materialThe organic phase was dried (Na2SO4)
filtrationfiltered
concentrationconcentrated

Sources & evidence

ORD record: ord-637a8308b7d547f7917a35b637d3051c
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09346782B2

Reaction notes

Loading…