Water → 4-(benzyloxy)-3-methyl-6-(pyridin-3-yl)-2-{[3-(tetrahydro-2H-pyran-4-ylmethoxy)phenoxy]methyl}quinoline

HRID 384465Notes

Reaction equation

HRID 384465 reaction equation
[CH2:1]([O:8][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16](Br)[CH:17]=2)[N:12]=[C:11]([CH2:20][O:21][C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH2:29][CH:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)[CH:23]=2)[C:10]=1[CH3:36])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N:37]1[CH:42]=[CH:41][CH:40]=[C:39](OB(O)O)[CH:38]=1.C(=O)([O-])[O-].[Na+].[Na+].O>O1CCOCC1.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>[CH2:1]([O:8][C:9]1[C:18]2[C:13](=[CH:14][CH:15]=[C:16]([C:39]3[CH:38]=[N:37][CH:42]=[CH:41][CH:40]=3)[CH:17]=2)[N:12]=[C:11]([CH2:20][O:21][C:22]2[CH:27]=[CH:26][CH:25]=[C:24]([O:28][CH2:29][CH:30]3[CH2:35][CH2:34][O:33][CH2:32][CH2:31]3)[CH:23]=2)[C:10]=1[CH3:36])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10340Sodium CarbonateHCID 184153773-Pyridylboric acidHCID 595270124-(benzyloxy)-6-bromo-3-methyl-2-{[3-(tetrahydro-2H-pyran-4-ylmethoxy)phenoxy]methyl}quinoline

Product 1

HCID 595273384-(benzyloxy)-3-methyl-6-(pyridin-3-yl)-2-{[3-(tetrahydro-2H-pyran-4-ylmethoxy)phenoxy]methyl}quinolineYield 88.6%

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 4-(benzyloxy)-6-bromo-3-methyl-2-{[3-(tetrahydro-2H-pyran-4-ylmethoxy)phenoxy]methyl}quinoline (300 mg) in dioxane (10 mL) were added pyridin-3-yl boric acid (135 mg), tetrakis(triphenylphosphine)palladium(0) (65 mg), and a 1M aqueous sodium carbonate solution (1.60 mL), followed by stirring at 80° C. for 2 hours. The reaction mixture was allowed to cool to room temperature, and water (20 mL) was added thereto, followed by extraction with chloroform (50 mL). The organic layer was washed sequentially with a saturated aqueous sodium hydrogen carbonate solution and saturated brine and then dried over anhydrous magnesium sulfate, and the solvent was evaporated. The residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=15/85) to obtain 4-(benzyloxy)-3-methyl-6-(pyridin-3-yl)-2-{[3-(tetrahydro-2H-pyran-4-ylmethoxy)phenoxy]methyl}quinoline (265 mg).

Workup

  1. temperatureto cool to room temperature
  2. extractionfollowed by extraction with chloroform (50 mL)
  3. washThe organic layer was washed sequentially with a saturated aqueous sodium hydrogen carbonate solution and saturated brine
  4. dry with materialdried over anhydrous magnesium sulfate
  5. customthe solvent was evaporated
  6. customThe residue was purified by silica gel column chromatography (eluent: hexane/ethyl acetate=15/85)

Sources & evidence

ORD record
ord-18c8c96124404da89803c03ffd4c024c
Source dataset
uspto-grants-2013_02
Patent number
US08367702B2

Reaction notes

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