Water → HCID 58456706, compound

HRID 2036135Notes

Reaction equation

HRID 2036135 reaction equation
[N:1]1[CH:6]=[CH:5][C:4](B(O)O)=[CH:3][CH:2]=1.Br[C:11]1[CH:12]=[C:13]([F:20])[C:14]([O:18][CH3:19])=[C:15]([F:17])[CH:16]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C)C=O.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>[F:17][C:15]1[CH:16]=[C:11]([C:4]2[CH:5]=[CH:6][N:1]=[CH:2][CH:3]=2)[CH:12]=[C:13]([F:20])[C:14]=1[O:18][CH3:19]

Participants

7

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 2734379(Pyridin-4-yl)boronic acidHCID 27732874-Bromo-2,6-difluoroanisole

Product 1

HCID 58456706HCID 58456706, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Procedure

In a microwave vial, a mixture of pyridin-4-ylboronic acid (160 mg, 1.3 mmol), 5-bromo-1,3-difluoro-2-methoxybenzene A5a (223 mg, 1 mmol) and Pd(PPh3)4 (58 mg, 0.05 mmol) is dissolved/suspended in dimethylformamide (3 mL). To the mixture are added cesium carbonate (978 mg, 3 mmol) and water (3 mL). The vial is sealed and subjected to microwave irradiation (150° C., 15 min). The mixture is filtered through a syringe filter and washed with ethyl acetate. Water is added and the mixture extracted with ethyl acetate (4×). The organic phase is dried over sodium sulfate and concentrated. The crude material is purified by flash chromatography (ethyl acetate/hexanes gradient) to afford 4-(3,5-difluoro-4-methoxyphenyl)pyridine A5b as a white solid: 1H-NMR (400 MHz, CDCl3) δ 8.69 (d, J=6 Hz, 2H), 7.44 (d, J=6 Hz, 2H), 7.22 (d, J=9.6 Hz, 2H), 4.09 (s, 3H); MS calcd. for C12H10F2NO ([M+H]+): 222.1, found: 222.1.

Workup

  1. customThe vial is sealed
  2. customsubjected to microwave irradiation (150° C., 15 min)
  3. filtrationThe mixture is filtered through a syringe
  4. filtrationfilter
  5. washwashed with ethyl acetate
  6. additionWater is added
  7. extractionthe mixture extracted with ethyl acetate (4×)
  8. dry with materialThe organic phase is dried over sodium sulfate
  9. concentrationconcentrated
  10. customThe crude material is purified by flash chromatography (ethyl acetate/hexanes gradient)

Sources & evidence

ORD record
ord-1e979396c8984d63b7c52912c3af2e32
Source dataset
uspto-grants-2013_11
Patent number
US08575168B2

Reaction notes

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