Water → HCID 22280146, compound

HRID 1063661Notes

Reaction equation

HRID 1063661 reaction equation
Br[C:2]1[C:7](C)=[CH:6][C:5]([CH3:9])=[CH:4][C:3]=1C.[OH:11][CH2:12]C1C=CC(B(O)O)=CC=1.[C:22](=[O:25])([O-])[O-:23].[Cs+].[Cs+].[CH2:28](N(CC)CC)C.[CH3:35][S:36](Cl)(=O)=O.ClC[C:42]1[CH:47]=[CH:46][C:45]([C:48]2[C:53]([CH3:54])=[CH:52][C:51]([CH3:55])=[CH:50][C:49]=2[CH3:56])=[CH:44][CH:43]=1.[OH2:57]>C(#N)C.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].CN(C=O)C.C1COCC1>[CH3:28][O:57][C:2]1[C:7]([S:36][CH2:35][C:42]2[CH:43]=[CH:44][C:45]([C:48]3[C:49]([CH3:56])=[CH:50][C:51]([CH3:55])=[CH:52][C:53]=3[CH3:54])=[CH:46][CH:47]=2)=[CH:6][C:5]([CH3:9])=[C:4]([CH:3]=1)[O:11][CH2:12][C:22]([OH:23])=[O:25]

Participants

11

Reactant 7

HCID 962WaterHCID 8471TriethylamineHCID 10796Cesium carbonate2×HCID 31297Methanesulfonyl chlorideHCID 684732-BromomesityleneHCID 27347064-(Hydroxymethyl)benzeneboronic acidHCID 22280117HCID 22280117, compound

Product 1

HCID 22280146HCID 22280146, compound

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6342AcetonitrileSolventHCID 21974620tetrahydrofuran N,N-dimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

2-Bromo-1,3,5-trimethyl-benzene (396 mg, 2mmol), 4-hydroxymethylphenylboronic acid (334 mg, 2.2 mmol), cesium carbonate (1.3 g, 4 mmol), and PdCl2(dppf) (82 mg, 0.1 mmol) were added to 5 ml of a 1:1 solution of DMF/THF. The reaction was flushed with nitrogen and heated to 90° C. for 1 h. The reaction was cooled, poured into diethyl ether and washed with water (2×10 ml), brine (1×10 ml) and dried over anhydrous sodium sulfate. The organic solution was filtered through silica gel, eluted with diethyl ether, and concentrated. The crude product was dissolved in 10 ml dichloromethane. Added to this solution were triethylamine (202 mg, 2 mmol) then methanesulfonyl chloride (184 mg, 1.6 mmol) and allowed to stir at ambient temperature for 18 h. The reaction was poured into water and extracted with methylene chloride. The organic solution was dried over anhydrous sodium sulfate, decanted and concentrated to provide the crude alkyl chloride. The product from Example 1D (387 mg, 1.6 mmol), the crude 4′-chloromethyl-2,4,6-trimethyl-biphenyl, and cesium carbonate (1 g, 3.06 mmol) were stirred in 10 ml acetonitrile for 3h, filtered, concentrated, and purified by normal phase chromatography to afford the title product. MS m/z 451 (M+1).

Workup

  1. customThe reaction was flushed with nitrogen
  2. temperatureThe reaction was cooled
  3. additionpoured into diethyl ether
  4. washwashed with water (2×10 ml), brine (1×10 ml)
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationThe organic solution was filtered through silica gel
  7. washeluted with diethyl ether
  8. concentrationconcentrated
  9. dissolutionThe crude product was dissolved in 10 ml dichloromethane
  10. additionAdded to this solution
  11. extractionextracted with methylene chloride
  12. dry with materialThe organic solution was dried over anhydrous sodium sulfate
  13. customdecanted
  14. concentrationconcentrated
  15. customto provide the crude alkyl chloride
  16. filtrationfiltered
  17. concentrationconcentrated
  18. custompurified by normal phase chromatography

Sources & evidence

ORD record
ord-5d9b5b1a1c234b77906caf399b0e8475
Source dataset
uspto-grants-2005_11
Patent number
US06964983B2

Reaction notes

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