4-Bromoanisole → HCID 11360273, compound

HRID 1825288Notes

Reaction equation

HRID 1825288 reaction equation
CC(C)([O-])C.[Na+].Br[C:8]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=1.[C:16]1([CH2:22][O:23][C:24]2[CH:25]=[C:26]3[C:31](=[CH:32][CH:33]=2)[C:30](=[O:34])[CH2:29][CH2:28][CH2:27]3)[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.O1CCOCC1>[OH:34][C:30]1[C:31]2[C:26](=[CH:25][C:24]([O:23][CH2:22][C:16]3[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=3)=[CH:33][CH:32]=2)[CH:27]=[CH:28][C:29]=1[C:8]1[CH:13]=[CH:12][C:11]([O:14][CH3:15])=[CH:10][CH:9]=1

Participants

7

Reactant 3

HCID 77304-BromoanisoleHCID 106822416-(benzyloxy)-3,4-dihydronaphthalen-1(2H)-oneHCID 23676156Sodium t-butoxide

Product 1

HCID 11360273HCID 11360273, compoundYield 40%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 634876Binap, (A+-)-CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

Twelve liters of 1,4-dioxane were vacuum degassed and then combined with sodium tert-butoxide (1523 g, 15.84 mol), 4-bromoanisole (1845 g, 9.86 mol) and 3,4-dihydro-6-(phenylmethoxy)-1(2H)-naphthalenone (1002 g, 3.97 mol). The resulting red slurry was again degassed by pulling vacuum and purging the system with nitrogen. Palladium acetate (8.90 g, 0.0396 mol) and 2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (25.9 g, 0.0416 mol) were added and the mixture was heated to 70° C. After 2.5 hours the temperature was increased to 100° C. and this temperature was maintained for an additional 5 hours. The mixture was allowed to cool to ambient temperature before quenching with 6 liters of 3 M HCl. The layers were allowed to separate and the aqueous phase was extracted with 2 liters of ethyl acetate. The organic phases were combined and dried with 500 g of sodium sulfate then concentrated to a red solid. The solid was combined with 4 liters of toluene and stirred at 60° C. for 1 hour then cooled to ambient temperature. The solids were collected by filtration, washed with toluene and dried in vacuo to provide 564 g (40%) of the title compound. H1 NMR (CDCl3, 500 MHz) 8.20 (d, J=9.1 Hz, 1H), 7.50 (d, J=7.3 Hz, 2H), 7.44 (d, J=8.7 Hz, 2H), 7.42 (t, J=7.3 Hz, 2H), 7.35 (m, 2H), 7.29 (d, J=8.5 Hz, 1H), 7.25 (dd, J=2.5, 9.1 Hz, 1H), 7.20 (d, J=2.5, 1H), 7.07 (d, J=8.7 Hz, 2H), 5.75 (s, 1H), 5.20 (s, 2H), 3.88 (s, 3H).

Workup

  1. customdegassed
  2. customThe resulting red slurry was again degassed
  3. custompurging the system with nitrogen
  4. temperatureAfter 2.5 hours the temperature was increased to 100° C.
  5. temperaturethis temperature was maintained for an additional 5 hours
  6. temperatureto cool to ambient temperature
  7. custombefore quenching with 6 liters of 3 M HCl
  8. customto separate
  9. extractionthe aqueous phase was extracted with 2 liters of ethyl acetate
  10. dry with materialdried with 500 g of sodium sulfate
  11. concentrationthen concentrated to a red solid
  12. temperaturethen cooled to ambient temperature
  13. filtrationThe solids were collected by filtration
  14. washwashed with toluene
  15. customdried in vacuo

Sources & evidence

ORD record
ord-5140a161e31c45e7a7752119c081ea73
Source dataset
uspto-grants-2006_05
Patent number
US07045628B2

Reaction notes

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