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

HRID 1882222
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HRID 1882222 반응식
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]
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참가 물질

6

반응물 4

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

생성물 1

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

시약·촉매·용매 1

HCID 312751,4-Dioxane용매

실험 절차

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.

후처리

  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)

출처 및 근거

ORD 기록
ord-4cea9d795e314085981f536cf9835931
출처 데이터셋
uspto-grants-2012_11
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08318939B2

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