Sodium Carbonate → methyl 6-(2-fluoro-5-methoxyphenyl)-5-((tetrahydro-2H-pyran-2-yl)oxy)nicotinate

HRID 709787Notes

Reaction equation

HRID 709787 reaction equation
Cl[C:2]1[C:11]([O:12][CH:13]2[CH2:18][CH2:17][CH2:16][CH2:15][O:14]2)=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][N:3]=1.[F:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][C:21]=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].O>[F:19][C:20]1[CH:25]=[CH:24][C:23]([O:26][CH3:27])=[CH:22][C:21]=1[C:2]1[C:11]([O:12][CH:13]2[CH2:18][CH2:17][CH2:16][CH2:15][O:14]2)=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][N:3]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 41572112-Fluoro-5-methoxyphenylboronic acidHCID 112698722-Dicyclohexylphosphino-2',6'-dimethoxybiphenylHCID 117759840methyl 6-chloro-5-((tetrahydro-2H-pyran-2-yl)oxy)nicotinate

Product 1

HCID 117760018methyl 6-(2-fluoro-5-methoxyphenyl)-5-((tetrahydro-2H-pyran-2-yl)oxy)nicotinateYield 64.2%

Reagents, catalysts & solvents 3

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
100 °C

Procedure

Under a nitrogen atmosphere, to a solution of methyl 6-chloro-5-((tetrahydro-2H-pyran-2-yl)oxy)nicotinate (546 mg) in toluene (6.7 mL) were added 2-fluoro-5-methoxyphenylboronic acid (512 mg), 2-dicyclohexylphosphino-2′,6′-dimethoxybiphenyl (132 mg), tris(dibenzylideneacetone)dipalladium(0) (74 mg) and 2.0 M aqueous sodium carbonate (3.0 mL) solution, and the mixture was stirred at 100° C. for 20 hr. The reaction mixture was poured into water, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, and dried over anhydrous sodium sulfate. The solvent was evaporated under reduced pressure, and the residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (466 mg) as a yellow oil.

Workup

  1. extractionthe mixture was extracted with ethyl acetate
  2. washThe extract was washed with saturated brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. customThe solvent was evaporated under reduced pressure
  5. customthe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-9ecc3fd971c243e783061526958db664
Source dataset
uspto-grants-2015_11
Patent number
US09181186B2

Reaction notes

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