Sodium Carbonate → 3-(Benzyloxy)-5-(((tert-butyldimethylsilyl)oxy)methyl)-2-(2-fluoro-5-methoxyphenyl)pyridine

HRID 709778Notes

Reaction equation

HRID 709778 reaction equation
[CH2:1]([O:8][C:9]1[C:10](Cl)=[N:11][CH:12]=[C:13]([CH2:15][O:16][Si:17]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18])[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[F:25][C:26]1[CH:31]=[CH:30][C:29]([O:32][CH3:33])=[CH:28][C:27]=1B(O)O.C1(P(C2CCCCC2)C2C=CC=CC=2C2C(OC)=CC=CC=2OC)CCCCC1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd]>[CH2:1]([O:8][C:9]1[C:10]([C:27]2[CH:28]=[C:29]([O:32][CH3:33])[CH:30]=[CH:31][C:26]=2[F:25])=[N:11][CH:12]=[C:13]([CH2:15][O:16][Si:17]([C:20]([CH3:23])([CH3:22])[CH3:21])([CH3:19])[CH3:18])[CH:14]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 41572112-Fluoro-5-methoxyphenylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 1317339153-(Benzyloxy)-5-(((tert-butyldimethylsilyl)oxy)methyl)-2-chloropyridine

Product 1

HCID 1317339163-(Benzyloxy)-5-(((tert-butyldimethylsilyl)oxy)methyl)-2-(2-fluoro-5-methoxyphenyl)pyridineYield 89.1%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 1140TolueneSolvent

Conditions

Temperature
90 °C

Procedure

Under an argon atmosphere, to a solution of 3-(benzyloxy)-5-(((tert-butyldimethylsilyl)oxy)methyl)-2-chloropyridine (2.53 g) in toluene (20 mL) were added 2-fluoro-5-methoxyphenylboronic acid (1.77 g), tris(dibenzylideneacetone)dipalladium(0) (255 mg), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (457 mg) and 2.0 M aqueous sodium carbonate solution (10.4 ml), and the mixture was stirred at 90° C. for 3 hr. The reaction mixture was filtered through celite, and water was added at room temperature. The reaction mixture was extracted with ethyl acetate, and the extract was washed with water and saturated brine, and dried over anhydrous magnesium sulfate, and the solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (2.81 g) as a pale-yellow oil.

Workup

  1. filtrationThe reaction mixture was filtered through celite, and water
  2. additionwas added at room temperature
  3. extractionThe reaction mixture was extracted with ethyl acetate
  4. washthe extract was washed with water and saturated brine
  5. dry with materialdried over anhydrous magnesium sulfate
  6. customthe solvent was evaporated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-2f70bfde51cd4fd6afeee335b558927e
Source dataset
uspto-grants-2015_11
Patent number
US09181186B2

Reaction notes

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