Potassium Carbonate → 4-Methoxy-2-fluoro-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)benzaldehyde

HRID 1057830Notes

Reaction equation

HRID 1057830 reaction equation
[F:1][C:2]1[C:9](S(C(F)(F)F)(=O)=O)=[C:8]([O:17][CH3:18])[CH:7]=[CH:6][C:3]=1[CH:4]=[O:5].[CH3:19][C:20]1[C:21](B(O)O)=[CH:22][C:23]2[C:24]([CH3:33])([CH3:32])[CH2:25][CH2:26][C:27]([CH3:31])([CH3:30])[C:28]=2[CH:29]=1.C(=O)([O-])[O-].[K+].[K+]>COCCOC.O.C(OCC)(=O)C.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>[CH3:18][O:17][C:8]1[CH:7]=[CH:6][C:3]([CH:4]=[O:5])=[C:2]([F:1])[C:9]=1[C:21]1[C:20]([CH3:19])=[CH:29][C:28]2[C:27]([CH3:31])([CH3:30])[CH2:26][CH2:25][C:24]([CH3:33])([CH3:32])[C:23]=2[CH:22]=1

Participants

8

Reactant 3

HCID 11430Potassium CarbonateHCID 10037535(3,5,5,8,8-Pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)boronic acidHCID 222683312-Fluoro-4-methoxy-3-trifluoromethanesulfonyl benzaldehyde

Product 1

HCID 222682874-Methoxy-2-fluoro-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)benzaldehydeYield 62%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 2-fluoro-4-methoxy-3-trifluoromethanesulfonyl benzaldehyde (1.21 g, 4.01 mmol), (3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)boronic acid (1.08 g, 4.41 mmol) and potassium carbonate (2.22 g, 16.04 mmol) in 1,2-dimethoxyethane (30 mL) and water (2 mL) was degassed with argon for 30 minutes. Tetrakis(triphenylphosphine)palladium(0) (0.23 g, 0.2 mmol) was added and the mixture heated at reflux under argon for 16 hours. The solution was cooled to room temperature, diluted with ethyl acetate and washed successively with water and brine, dried over anhydrous magnesium sulfate, filtered and evaporated. The residue was chromatographed on silica gel (Biotage, eluent: ethyl acetate/hexane, 0.5:8.5) to give 0.87 g of 4-methoxy-2-fluoro-3-(3,5,5,8,8-pentamethyl-5,6,7,8-tetrahydronaphthalen-2-yl)benzaldehyde (62%). 1H NMR (500 MHz; CDCl3): δ1.26 (s, 6H), 1.32 (s, 6H), 1.69 (s, 4H), 2.07 (s, 3H), 3.85 (s, 3H), 7.07 (d, J=8.8 Hz, 1H), 7.07 (s, 1H), 7.19 (s, 1H), 7.90 (t, J=8.8 Hz, 1H), 10.25 (s, 1H).

Workup

  1. customwas degassed with argon for 30 minutes
  2. temperaturethe mixture heated
  3. temperatureat reflux under argon for 16 hours
  4. washwashed successively with water and brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was chromatographed on silica gel (Biotage, eluent: ethyl acetate/hexane, 0.5:8.5)

Sources & evidence

ORD record
ord-7a06cf812eca4403af78e9c6c3c79be1
Source dataset
uspto-grants-2003_02
Patent number
US06515003B1

Reaction notes

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