Triethylamine → 2-Fluoro-4-methoxy-3-(1,4,4,6-tetramethyl-2-oxo-1,2,3,4-tetrahydro-quinolin-7-yl)-benzaldehyde

HRID 2212586

Reaction equation

HRID 2212586 reaction equation
Br[C:2]1[CH:11]=[C:10]2[C:5]([C:6]([CH3:15])([CH3:14])[CH2:7][C:8](=[O:13])[N:9]2[CH3:12])=[CH:4][C:3]=1[CH3:16].C(N(CC)CC)C.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.[B]1OC(C)(C)C(C)(C)O1.O.O.O.O.O.O.O.O.[OH-].[Ba+2].[OH-].[F:69][C:70]1[C:77](I)=[C:76]([O:79][CH3:80])[CH:75]=[CH:74][C:71]=1[CH:72]=[O:73]>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[F:69][C:70]1[C:77]([C:2]2[CH:11]=[C:10]3[C:5]([C:6]([CH3:15])([CH3:14])[CH2:7][C:8](=[O:13])[N:9]3[CH3:12])=[CH:4][C:3]=2[CH3:16])=[C:76]([O:79][CH3:80])[CH:75]=[CH:74][C:71]=1[CH:72]=[O:73]

Participants

10

Reactant 6

HCID 8471TriethylamineHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 6364989PinacolboraneHCID 17749109Barium hydroxide, octahydrateHCID 219664297-bromo-1,4,4,6-tetramethyl-3,4-dihydro-1H-quinoline-2-oneHCID 219664772-Fluoro-3-iodo-4-methoxybenzaldehyde

Product 1

HCID 219664782-Fluoro-4-methoxy-3-(1,4,4,6-tetramethyl-2-oxo-1,2,3,4-tetrahydro-quinolin-7-yl)-benzaldehydeYield 52%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
80 °C

Procedure

To a solution of 7-bromo-1,4,4,6-tetramethyl-3,4-dihydro- 1H-quinoline-2-one (example 1d) (0.96 g, 3.40 mmol) in dioxane (2 mL) were added under argon, triethylamine 1.9 mL, 13.61 mmol), palladium acetate (38 mg, 0.17 mmol), 2-(dicyclohexylphosphino) biphenyl (238 mg, 0.68 mmol) and pinacolborane (1M in THF, 10.2 mL, 10.2 mmol). The mixture was stirred at 80° C. for 1 hr 45 min, then cooled to room temperature. Water (1.5 mL), barium hydroxide octahydrate (3.22 g, 10.20 mmol) and 2-Fluoro-3-iodo-4-methoxy benzaldehyde dissolved in dioxane (7 mL) were successively added and the mixture heated at 100° C. for 13 hrs. The mixture was cooled to room temperature and filtered over celite. Brine was added and the aqueous layer was extracted with dichloromethane. The organic extract was washed successively with water and brine, dried over anhydrous magnesium sulfate, filtered and evaporated. The residue was purified on silica gel (20% to 30% ethyl acetate in hexane) to give 0.63 g of 2-Fluoro-4-methoxy-3-(1,4,4,6-tetramethyl-2-oxo-1,2,3,4-tetrahydro-quinolin-7-yl)-benzaldehyde (52%). 1H NMR (300 MHz; CDCl3): 1.33 (s, 3 H), 1.35 (s, 3 H), 2.09 (s, 3 H), 2.54 (s, 2 H), 3.35 (s, 3 H), 3.87 (s, 3 H), 6.79 (s, 1 H), 6.92 (d, J=8.7 Hz, 1 H), 7.21 (s, 1 H), 7.94 (t, J=8.7 Hz, 1 H), 10.25 (s, 1 H).

Workup

  1. temperaturecooled to room temperature
  2. additionwere successively added
  3. temperaturethe mixture heated at 100° C. for 13 hrs
  4. temperatureThe mixture was cooled to room temperature
  5. filtrationfiltered over celite
  6. additionBrine was added
  7. extractionthe aqueous layer was extracted with dichloromethane
  8. extractionThe organic extract
  9. washwas washed successively with water and brine
  10. dry with materialdried over anhydrous magnesium sulfate
  11. filtrationfiltered
  12. customevaporated
  13. customThe residue was purified on silica gel (20% to 30% ethyl acetate in hexane)

Sources & evidence

ORD record
ord-373a76e3126641f6916979af7c80dd7c
Source dataset
uspto-grants-2006_09
Patent number
US07102000B2

Linked notes

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