Cesium carbonate → HCID 22648150, compound

HRID 394164Notes

Reaction equation

HRID 394164 reaction equation
Cl[C:2]1[C:7]([CH3:8])=[CH:6][C:5]([N+:9]([O-:11])=[O:10])=[CH:4][N:3]=1.[F:12][C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=1B(O)O.C([O-])([O-])=O.[Cs+].[Cs+]>CN(C=O)C.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:12][C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=1[C:2]1[C:7]([CH3:8])=[CH:6][C:5]([N+:9]([O-:11])=[O:10])=[CH:4][N:3]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 896482-Chloro-3-methyl-5-nitropyridineHCID 27343342,4-Difluorophenylboronic acid

Product 1

HCID 22648150HCID 22648150, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

To a stirred solution of 2-chloro-3-methyl-5-nitropyridine (prepared according to the procedure of Hawkins and Roe, J. Am. Chem. Soc., page 330, 1948) (17.6 g, 102 mmol, 1 eq.) in DMF (220 mL) was added 2,4-difluorobenzeneboronic acid (16.16 g, 102 mmol, 1 eq.) followed by Cs2CO3 (41.1 g, 122.7 mmol, 1.2 eq). The mixture was degassed with argon. To the mixture was added tetrakis(triphenylphosphine)palladium(0) (2.5 g, 2 mmol, 0.02 eq). The mixture was degassed with argon and then heated to 100° C. under argon. After 18 h the mixture was cooled. The mixture was filtered and the filtrate concentrated under reduced pressure. The filtrate was partitioned between water and ethyl acetate. The aqueous layer was extracted several times with ethyl acetate. The organic extracts were combined, dried over anhydrous Na2SO4, filtered and concentrated. The material was purified by flash column chromatography eluting with 5:1 hekanes/acetone giving 7.5 g 2-(2,4-difluorophenyl)-3-methyl-5-nitropyridine. Mass spectrum (ESI) 251.3 (M+1). 1H NMR (500 MHz, CDCl3) δCHCl3: 9.35 (1H, s); 8.42 (1H, s); 7.47 (1H,m); 7.07 (1H, m); 6.97 (1H, m); 2.41 (3H, s).

Workup

  1. customThe mixture was degassed with argon
  2. customThe mixture was degassed with argon
  3. temperatureAfter 18 h the mixture was cooled
  4. filtrationThe mixture was filtered
  5. concentrationthe filtrate concentrated under reduced pressure
  6. customThe filtrate was partitioned between water and ethyl acetate
  7. extractionThe aqueous layer was extracted several times with ethyl acetate
  8. dry with materialdried over anhydrous Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated
  11. customThe material was purified by flash column chromatography
  12. washeluting with 5:1 hekanes/acetone giving 7.5 g 2-(2,4-difluorophenyl)-3-methyl-5-nitropyridine

Sources & evidence

ORD record
ord-476aeb34230d448482429437f79a6d97
Source dataset
uspto-grants-2004_10
Patent number
US06809199B2

Reaction notes

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