Sodium Carbonate → 3-(3-Tert-butyl-4-difluoromethoxy-phenyl)-2-methoxy-pyridine

HRID 2390791Notes

Reaction equation

HRID 2390791 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([O:8][CH:9]([F:11])[F:10])=[C:4]([C:12]([CH3:15])([CH3:14])[CH3:13])[CH:3]=1.[CH3:16][O:17][C:18]1[C:23](B(O)O)=[CH:22][CH:21]=[CH:20][N:19]=1.C([O-])([O-])=O.[Na+].[Na+]>CO.C(Cl)Cl.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>[C:12]([C:4]1[CH:3]=[C:2]([C:23]2[C:18]([O:17][CH3:16])=[N:19][CH:20]=[CH:21][CH:22]=2)[CH:7]=[CH:6][C:5]=1[O:8][CH:9]([F:11])[F:10])([CH3:15])([CH3:14])[CH3:13]

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 2762709(2-Methoxypyridin-3-yl)boronic acidHCID 672864304-Bromo-2-tert-butyl-difluoromethoxy-benzene

Product 1

HCID 670700073-(3-Tert-butyl-4-difluoromethoxy-phenyl)-2-methoxy-pyridineYield 58%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
115 °C

Procedure

step 2—A sealed tube containing 20 (129 mg, 0.464 mmol), 2-methoxy-3-pyridine boronic acid (37, 108 mg, 0.706 mmol, CASRN 163105-90-6), Pd(PPh3)4 (39 mg, 0.034 mmol) and Na2CO3 (147 mg, 1.387 mmol) in a mixture of MeOH (3 mL) and DCM (1 mL) was heated in a microwave synthesizer at 115° C. for 30 min. The organic volatiles were removed under reduced pressure. The residue was partitioned between EtOAc and water. The organic layer was washed with brine, dried (Na2SO4), filtered and concentrated. The crude residue was purified by SiO2 chromatography eluting with a EtOAc/hexane gradient (0 to 5% EtOAc) to afford 82 mg (58%) of 3-(3-tert-butyl-4-difluoromethoxy-phenyl)-2-methoxy-pyridine (22) as an oil.

Workup

  1. customstep 2—A sealed tube
  2. customThe organic volatiles were removed under reduced pressure
  3. customThe residue was partitioned between EtOAc and water
  4. washThe organic layer was washed with brine
  5. dry with materialdried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe crude residue was purified by SiO2 chromatography
  9. washeluting with a EtOAc/hexane gradient (0 to 5% EtOAc)

Sources & evidence

ORD record
ord-9193624c7cf446d3849efe39f7b72495
Source dataset
uspto-grants-2012_09
Patent number
US08273773B2

Reaction notes

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