Ammonium Chloride → 7-Methoxy-3-[2-(4-methoxy-benzyloxy)-pyridin-3-yl]-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one

HRID 2275289Notes

Reaction equation

HRID 2275289 reaction equation
[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH2:7][CH2:8][C:9](=[O:15])[C:10]2([CH3:14])[CH3:13])=[CH:5][CH:4]=1.Br[C:17]1[C:18]([O:23][CH2:24][C:25]2[CH:30]=[CH:29][C:28]([O:31][CH3:32])=[CH:27][CH:26]=2)=[N:19][CH:20]=[CH:21][CH:22]=1.CC(C)([O-])C.[Na+].F[B-](F)(F)F.[H+].C(P(C(C)(C)C)C(C)(C)C)(C)(C)C.[Cl-].[NH4+]>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1COCC1.C1(C)C=CC=CC=1>[CH3:1][O:2][C:3]1[CH:12]=[C:11]2[C:6]([CH2:7][CH:8]([C:17]3[C:18]([O:23][CH2:24][C:25]4[CH:26]=[CH:27][C:28]([O:31][CH3:32])=[CH:29][CH:30]=4)=[N:19][CH:20]=[CH:21][CH:22]=3)[C:9](=[O:15])[C:10]2([CH3:13])[CH3:14])=[CH:5][CH:4]=1

Participants

9

Reactant 5

HCID 25517Ammonium ChlorideHCID 130110077-Methoxy-1,1-dimethyl-3,4-dihydronaphthalen-2(1H)-one2×HCID 23676156Sodium t-butoxideHCID 613744983-Bromo-2-[(4-methoxyphenyl)methoxy]pyridineHCID 118705180Tris(tert-butyl)phosphonium tetrafluoroborate

Product 1

HCID 668353157-Methoxy-3-[2-(4-methoxy-benzyloxy)-pyridin-3-yl]-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-oneYield 8.1%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
90 °C

Procedure

To 7-methoxy-1,1-dimethyl-3,4-dihydro-1H-naphthalen-2-one (Compound A2, 845 mg), 3-bromo-2-(4-methoxy-benzyloxy)-pyridine (Compound GT15-15, 1.46 g), sodium t-butoxide (597 mg), palladium acetate (18.6 mg) and tri-tert-butylphosphine tetrafluoroboric acid (21 mg), toluene (10 ml) and THF (2 ml) were added and the mixture was stirred and heated at 90° C. for 2.5 hrs under nitrogen atmosphere. After cooling, the reaction mixture was added with saturated aqueous solution of ammonium chloride, and then extracted with ethyl acetate. The organic layer was washed with saturated brine, and the residues obtained after concentration under reduced pressure were purified by silica gel column (ethyl acetate/hexane) to obtain the title compound (140 mg, 8%).

Workup

  1. temperatureAfter cooling
  2. extractionextracted with ethyl acetate
  3. washThe organic layer was washed with saturated brine
  4. customthe residues obtained
  5. concentrationafter concentration under reduced pressure
  6. customwere purified by silica gel column (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-68d14d23f3ce49f1868aa28b5237f6a1
Source dataset
uspto-grants-2015_09
Patent number
US09126931B2

Reaction notes

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