1-Methyl-1H-1,2,3-triazole-5-carbaldehyde → (4-Chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinolin-6-yl)(1-methyl-1H-1,2,3-triazol-5-yl)methanol

HRID 526842Notes

Reaction equation

Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([O:12][CH3:13])[C:6]([CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=1)=[C:5]2[Cl:25].[Li]CCCC.[CH3:31][N:32]1[C:36]([CH:37]=[O:38])=[CH:35][N:34]=[N:33]1>C1COCC1>[Cl:25][C:5]1[C:4]2[C:9](=[CH:10][CH:11]=[C:2]([CH:37]([C:36]3[N:32]([CH3:31])[N:33]=[N:34][CH:35]=3)[OH:38])[CH:3]=2)[N:8]=[C:7]([O:12][CH3:13])[C:6]=1[CH2:14][C:15]1[CH:20]=[CH:19][C:18]([C:21]([F:24])([F:23])[F:22])=[CH:17][CH:16]=1

Participants

Conditions

Temperature: -20 °C

Procedure

To a flask containing 6-bromo-4-chloro-2-methoxy-3-(4-(trifluoromethyl)benzyl)quinoline (1.45 g, 3.37 mmol, Intermediate 5: step d) was added THF (25 mL) and the solution was cooled to −75° C. n-BuLi (2.5 M in hexanes, 1.3 mL, 3.25 mmol) was then added dropwise. After 2 minutes, 1-methyl-1H-1,2,3-triazole-5-carbaldehyde (580 mg, 5.22 mmol, in 3 mL THF) was introduced. The reaction mixture was allowed to warm to −20° C. over 45 minutes at which time the reaction was quenched with aqueous NH4Cl solution. The aqueous portion was extracted with EtOAc (5×40 mL) and the combined organics were washed with brine, dried over MgSO4, filtered and concentrated to dryness. Chromatography on silica gel (5% CH3CN-DCM increasing to 30% CH3CN+2% MeOH) provided the title compound as an off white amorphous solid.

Workup

additionwas then added dropwise
customwas quenched with aqueous NH4Cl solution
extractionThe aqueous portion was extracted with EtOAc (5×40 mL)
washthe combined organics were washed with brine
dry with materialdried over MgSO4
filtrationfiltered
concentrationconcentrated to dryness

Sources & evidence

ORD record: ord-7ef64f325c504f5d9fb126dc6c803440
Source dataset: uspto-grants-2016_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09346782B2

Reaction notes

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