2-Bromopyridine → HCID 21099415, compound

HRID 2376973Notes

Reaction equation

HRID 2376973 reaction equation
C([Li])CCC.Br[C:7]1[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=1.Br[C:14]1[CH:15]=[C:16]([S:20]([C:23]2[CH:28]=[CH:27][C:26](/[CH:29]=[CH:30]/[C:31]3[CH:36]=[CH:35][C:34]([F:37])=[CH:33][C:32]=3[F:38])=[CH:25][CH:24]=2)(=[O:22])=[O:21])[CH:17]=[CH:18][CH:19]=1>O1CCCC1.[Cl-].[Zn+2].[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>[F:38][C:32]1[CH:33]=[C:34]([F:37])[CH:35]=[CH:36][C:31]=1/[CH:30]=[CH:29]/[C:26]1[CH:27]=[CH:28][C:23]([S:20]([C:16]2[CH:17]=[C:18]([C:7]3[CH:12]=[CH:11][CH:10]=[CH:9][N:8]=3)[CH:19]=[CH:14][CH:15]=2)(=[O:22])=[O:21])=[CH:24][CH:25]=1

Participants

7

Reactant 3

HCID 79732-BromopyridineHCID 21099399HCID 21099399, compoundHCID 178418339Butyllithium

Product 1

HCID 21099415HCID 21099415, compoundYield 10%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Butyllithium (1.6M in hexanes, 0.3 mL, 0.48 mmol) was added to a rapidly stirred solution of 2-bromopyridine (44 μL, 0.46 mmol) in tetrahydrofuran (1.2 mL) at −78° C. After 45 minutes, zinc chloride (1.0M in diethyl ether, 1.38 mL, 1.38 mmol) was added. The mixture was warmed to room temperature, tetrakis(triphenylphosphine)palladium(0) (27 mg) and 1-((E)-2-{4-[(3-bromophenyl)sulfonyl]phenyl}vinyl)-2,4-difluorobenzene (Example 109; 100 mg, 0.23 mmol) were added and the reaction heated to reflux overnight. The cooled reaction mixture was partitioned between ethyl acetate and 10% aqueous ethylenediaminetetraacetic acid, disodium salt. The organic layer was dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash column chromatography on silica, eluting with 35% ethyl acetate/isohexane, to yield the title compound as a white solid (10 mg, 10%). δH (400 MHz, CDCl3): 8.69 (1H, d, J=4.7 Hz), 8.56 (1H, t, J=1.7 Hz), 8.23 (1H, d, J=7.8 Hz), 7.98-7.94 (3H, m), 7.80-7.74 (2H, m), 7.62-7.50 (4H, m), 7.29-7.23 (2H, m), 7.07 (1H, d, J=16.5 Hz), 6.90-6.80 (2H, m). m/z (ES+) 434 [MH+].

Workup

  1. temperaturethe reaction heated
  2. temperatureto reflux overnight
  3. customThe cooled reaction mixture
  4. customwas partitioned between ethyl acetate and 10% aqueous ethylenediaminetetraacetic acid, disodium salt
  5. dry with materialThe organic layer was dried over Na2SO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by flash column chromatography on silica
  8. washeluting with 35% ethyl acetate/isohexane

Sources & evidence

ORD record
ord-ea9521e2a3df46b38f500cafd2332e2a
Source dataset
uspto-grants-2008_12
Patent number
US07468393B2

Reaction notes

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