Potassium Carbonate → 3-(1-Ethyl-4,4,6-trimethyl-2-oxo-1,2,3,4-tetrahydro-quinolin-7-yl)-4-trifluoromethoxy-benzaldehyde

HRID 883068Notes

Reaction equation

HRID 883068 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([C:6]([CH3:16])([CH3:15])[CH2:7][C:8](=[O:14])[N:9]2[CH2:12][CH3:13])=[CH:4][C:3]=1[CH3:17].[F:18][C:19]([F:33])([F:32])[O:20][C:21]1[CH:26]=[CH:25][C:24]([CH:27]=[O:28])=[CH:23][C:22]=1B(O)O.C(=O)([O-])[O-].[K+].[K+]>C1(C)C=CC=CC=1.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>[CH2:12]([N:9]1[C:10]2[C:5](=[CH:4][C:3]([CH3:17])=[C:2]([C:26]3[CH:25]=[C:24]([CH:23]=[CH:22][C:21]=3[O:20][C:19]([F:18])([F:32])[F:33])[CH:27]=[O:28])[CH:11]=2)[C:6]([CH3:16])([CH3:15])[CH2:7][C:8]1=[O:14])[CH3:13]

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 219664285-Formyl-2-(trifluoromethoxy)benzeneboronic acidHCID 219664867-Bromo-1-ethyl-4,4,6-trimethyl-3,4-dihydro-1H-quinolin-2-one

Product 1

HCID 112234493-(1-Ethyl-4,4,6-trimethyl-2-oxo-1,2,3,4-tetrahydro-quinolin-7-yl)-4-trifluoromethoxy-benzaldehydeYield 64.9%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 1140TolueneSolvent2×

Procedure

A solution of Compound 1A (1 g, 3.38 mmol) in 17 mL of toluene was added to a flask containing 2-trifluoromethoxy-5-formyl-phenyl boronic acid (0.95 g, 4.05 mmol), prepared by the procedure described in WO 03/075924, and tetrakis(triphenylphosphine)palladium(0) (195 mg, 0.17 mmol) in 4 mL of toluene. Next, 3.4 mL of a 2M solution of potassium carbonate was added and the reaction heated to reflux for four hours, after which the reaction was cooled and partitioned between ethyl acetate (100 mL) and water (50 mL). The aqueous layer was further extracted with ethyl acetate (2×100 mL) and the combined organic layers were dried with sodium sulfate, filtered, stripped and purified via flash chromatography (15% EtOAc/hexanes) to afford 890 mg of product Compound 2A (65%). MS (electrospray): mass calculated for C22H22F3NO3, 405.16; m/z found 406.2, [M+H]+.

Workup

  1. customprepared by the procedure
  2. temperaturethe reaction heated
  3. temperatureto reflux for four hours
  4. temperatureafter which the reaction was cooled
  5. custompartitioned between ethyl acetate (100 mL) and water (50 mL)
  6. extractionThe aqueous layer was further extracted with ethyl acetate (2×100 mL)
  7. dry with materialthe combined organic layers were dried with sodium sulfate
  8. filtrationfiltered
  9. custompurified via flash chromatography (15% EtOAc/hexanes)

Sources & evidence

ORD record
ord-d00facb0ec3e4af89f6184b071f9c897
Source dataset
uspto-grants-2012_08
Patent number
US08236819B2

Reaction notes

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