Carbonic Acid → 5-Chloro-2-(2-(trifluoromethyl)phenyl)quinoline-3-carbaldehyde

HRID 2074517Notes

Reaction equation

HRID 2074517 reaction equation
Cl[C:2]1[C:11]([CH:12]=[O:13])=[CH:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][C:8]=2[Cl:14])[N:3]=1.[F:15][C:16]([F:27])([F:26])[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][C:18]=1B(O)O.C(O)(O)=O>CC#N.O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:14][C:8]1[CH:7]=[CH:6][CH:5]=[C:4]2[C:9]=1[CH:10]=[C:11]([CH:12]=[O:13])[C:2]([C:18]1[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=1[C:16]([F:27])([F:26])[F:15])=[N:3]2

Participants

6

Reactant 3

HCID 767Carbonic AcidHCID 27343872-(Trifluoromethyl)benzeneboronic acidHCID 157075292,5-Dichloroquinoline-3-carbaldehyde

Product 1

HCID 575561835-Chloro-2-(2-(trifluoromethyl)phenyl)quinoline-3-carbaldehyde

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 18373917Acetonitrile--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

A mixture of 2,5-dichloroquinoline-3-carbaldehyde (1.9948 g, 8.8243 mmol), 2-(trifluoromethyl)phenylboronic acid (1.8436 g, 9.7067 mmol), tetrakis(triphenylphosphine)palladium (0.50985 g, 0.44121 mmol), and sodium carbonate anhydrous (4.6763 g, 44.121 mmol) in 88 mL of CH3CN—H2O (3:1) was stirred at 100° C. After 5 hr, the mixture was cooled to room temperature and partitioned between EtOAc (100 mL) and water (100 mL). The organic layer was washed with brine (50 mL×2), dried over MgSO4, filtered, and concentrated under reduced pressure to give a red syrup. The red syrup was purified by silica gel column chromatography on a 80 g of Redi-Sep™ column using 0 to 50% gradient of EtOAc in hexane over 25 min and then 50% isocratic of EtOAc for 30 min as eluent to give 5-chloro-2-(2-(trifluoromethyl)phenyl)quinoline-3-carbaldehyde as a light-yellow solid: 1H NMR (400 MHz, DMSO-d6) δ ppm 10.01 (1 H, s), 9.19 (1H, d, J=1.0 Hz), 8.08-8.14 (1 H, m), 7.97-8.03 (2 H, m), 7.89-7.95 (1 H, m), 7.73-7.84 (2 H, m), 7.55-7.61 (1 H, m); LC-MS (ESI) m/z 336.1 [M+H]+.

Workup

  1. temperaturethe mixture was cooled to room temperature
  2. custompartitioned between EtOAc (100 mL) and water (100 mL)
  3. washThe organic layer was washed with brine (50 mL×2)
  4. dry with materialdried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto give a red syrup
  8. customThe red syrup was purified by silica gel column chromatography on a 80 g of Redi-Sep™ column
  9. customover 25 min

Sources & evidence

ORD record
ord-12b667355f3a4d74a02b885b38cb1be3
Source dataset
uspto-grants-2011_04
Patent number
US07919498B2

Reaction notes

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