Cesium carbonate → 3-(3'-(Ethylsulfonyl)-4-methyl-3-nitro-5-(trifluoromethyl)biphenyl-2-yl)-2-fluoro-5-methylpyridine

HRID 1882222Notes

Reaction equation

HRID 1882222 reaction equation
Cl[C:2]1[C:7]([C:8]2[C:9]([F:15])=[N:10][CH:11]=[C:12]([CH3:14])[CH:13]=2)=[C:6]([N+:16]([O-:18])=[O:17])[C:5]([CH3:19])=[C:4]([C:20]([F:23])([F:22])[F:21])[CH:3]=1.[CH2:24]([S:26]([C:29]1[CH:30]=[C:31](B(O)O)[CH:32]=[CH:33][CH:34]=1)(=[O:28])=[O:27])[CH3:25].C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1>[CH2:24]([S:26]([C:29]1[CH:34]=[C:33]([C:2]2[CH:3]=[C:4]([C:20]([F:23])([F:21])[F:22])[C:5]([CH3:19])=[C:6]([N+:16]([O-:18])=[O:17])[C:7]=2[C:8]2[C:9]([F:15])=[N:10][CH:11]=[C:12]([CH3:14])[CH:13]=2)[CH:32]=[CH:31][CH:30]=1)(=[O:27])=[O:28])[CH3:25]

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 75806TricyclohexylphosphineHCID 164271023-Ethylsulfonylphenylboronic acidHCID 588800743-(6-Chloro-3-methyl-2-nitro-4-(trifluoromethyl)phenyl)-2-fluoro-5-methylpyridine

Product 1

HCID 249640503-(3'-(Ethylsulfonyl)-4-methyl-3-nitro-5-(trifluoromethyl)biphenyl-2-yl)-2-fluoro-5-methylpyridineYield 78.3%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

A mixture of 3-(6-chloro-3-methyl-2-nitro-4-(trifluoromethyl)phenyl)-2-fluoro-5-methylpyridine (6.0 g, 17.2 mmol), 3-ethylsulfonylphenylboronic acid (4.79 g, 22.4 mmol), bis(dibenzylidineacetone)Pd(0) (1.48 g, 2.6 mmol), tricyclohexylphosphine (1.45 g, 5.2 mmol), Cs2CO3 (14.0 g, 43 mmol), and dioxane (60 mL) was heated at reflux for 4.5 hr. After completion the reaction was cooled to room temperature, filtered, rinsed with dioxane, and concentrated in vacuo. The resulting oil was reconstituted in EtOAc (75 mL) washed with H2O (1×30 mL) and brine (1×30 mL), dried (MgSO4), and concentrated in vacuo. Purification by silica gel chromatography (4:1 hexanes/EtOAc) gave 6.5 g (78%) of the title compound as a tan solid. 1H NMR (400 MHz, DMSO-d6): δ 8.15 (s, 1H), 8.04 (s, 1H), 7.90-7.93 (m, 1H), 7.80-7.82 (m, 1H), 7.60-7.70 (m, 3H), 3.1-3.2 (m, 2H), 2.49 (s, 3H), 2.25 (s, 3H), 0.85 (t, 3H). MS (ES) [m+H] calc'd for C22H18F4N2O4S, 483; found 483.3.

Workup

  1. temperaturewas heated
  2. temperatureat reflux for 4.5 hr
  3. filtrationfiltered
  4. washrinsed with dioxane
  5. concentrationconcentrated in vacuo
  6. washwashed with H2O (1×30 mL) and brine (1×30 mL)
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customPurification by silica gel chromatography (4:1 hexanes/EtOAc)

Sources & evidence

ORD record
ord-4cea9d795e314085981f536cf9835931
Source dataset
uspto-grants-2012_11
Patent number
US08318939B2

Reaction notes

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