Triethylamine → 7-[5-Formyl-2-trifluoromethoxy-phenyl]-3,3-dimethyl-2,3-dihydro-benzofuran-5-carboxylic acid dimethylamide

HRID 460292

Reaction equation

HRID 460292 reaction equation
[CH3:1][N:2]([CH3:17])[C:3]([C:5]1[CH:6]=[C:7](Br)[C:8]2[O:12][CH2:11][C:10]([CH3:14])([CH3:13])[C:9]=2[CH:15]=1)=[O:4].C(N(CC)CC)C.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2)CCCCC1.[B]1OC(C)(C)C(C)(C)O1.Br[C:60]1[CH:61]=[C:62]([CH:65]=[CH:66][C:67]=1[O:68][C:69]([F:72])([F:71])[F:70])[CH:63]=[O:64]>O1CCOCC1.C(OCC)(=O)C.CC([O-])=O.CC([O-])=O.[Pd+2].O>[CH3:1][N:2]([CH3:17])[C:3]([C:5]1[CH:6]=[C:7]([C:60]2[CH:61]=[C:62]([CH:63]=[O:64])[CH:65]=[CH:66][C:67]=2[O:68][C:69]([F:70])([F:72])[F:71])[C:8]2[O:12][CH2:11][C:10]([CH3:14])([CH3:13])[C:9]=2[CH:15]=1)=[O:4]

Participants

10

Reactant 5

HCID 8471TriethylamineHCID 27342162-(Dicyclohexylphosphino)biphenylHCID 6364989PinacolboraneHCID 131504163-Bromo-4-(trifluoromethoxy)benzaldehydeHCID 695216765-Benzofurancarboxamide, 7-bromo-2,3-dihydro-N,N,3,3-tetramethyl-

Product 1

HCID 865888657-[5-Formyl-2-trifluoromethoxy-phenyl]-3,3-dimethyl-2,3-dihydro-benzofuran-5-carboxylic acid dimethylamideYield 50%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent2×

Conditions

Temperature
80 °C

Procedure

To a solution of 7-bromo-3,3-dimethyl-2,3-dihydro-benzofuran-5-carboxylic acid dimethylamide (437 mg, 1.46 mmol) in dioxane (4 mL), were added under argon, triethylamine (0.82 mL, 5.86 mmol), Pd(OAc)2 (16 mg, 0.07 mmol), 2-(dicyclohexylphosphino)biphenyl (103 mg, 0.29 mmol) and pinacolborane (0.64 mL, 4.40 mmol) dropwise. The mixture was heated at 80° C. under argon for 2 hrs then cooled to room temperature. Water (0.5 mL) was added dropwise, then Ba(OH)2.8H2O (1.38 g, 4.40 mmol) followed by 3-bromo-4-trifluoromethoxy benzaldehyde (example 1h) (473 mg, 1.76 mmol) dissolved in dioxane (1.2 mL). The mixture was refluxed for 4 hours then cooled to room temperature, diluted with ethyl acetate and filtered over celite. The solution was further washed with water and brine, dried over anhydrous magnesium sulfate, filtered and evaporated. The residue was purified on silica gel (5% methanol in dichloromethane) to give 264 mg of 7-[5-formyl-2-trifluoromethoxy-phenyl]-3,3-dimethyl-2,3-dihydro-benzofuran-5-carboxylic acid dimethylamide (containing 50% of 3,3-dimethyl-2,3-dihydro-benzofuran-5-carboxylic acid dimethylamide as determined by 1H NMR) use as this in the next step.

Workup

  1. temperaturethen cooled to room temperature
  2. temperatureThe mixture was refluxed for 4 hours
  3. temperaturethen cooled to room temperature
  4. filtrationfiltered over celite
  5. washThe solution was further washed with water and brine
  6. dry with materialdried over anhydrous magnesium sulfate
  7. filtrationfiltered
  8. customevaporated
  9. customThe residue was purified on silica gel (5% methanol in dichloromethane)

Sources & evidence

ORD record
ord-6908386d08bc40eab6b69f5163dec099
Source dataset
uspto-grants-2007_03
Patent number
US07196108B2

Linked notes

Loading…