Ethylene → 4'-Methyl-5-thiazol-2-yl-biphenyl-3-carboxylic acid methyl ester

HRID 1888898Notes

Reaction equation

HRID 1888898 reaction equation
BrCCBr.C=C.C[Si](Cl)(C)C.Br[C:13]1[S:14][CH:15]=[CH:16][N:17]=1.[CH3:18][O:19][C:20]([C:22]1[CH:23]=[C:24]([C:29]2[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][CH:30]=2)[CH:25]=[C:26](I)[CH:27]=1)=[O:21]>C1COCC1.[Zn].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>[CH3:18][O:19][C:20]([C:22]1[CH:23]=[C:24]([C:29]2[CH:30]=[CH:31][C:32]([CH3:35])=[CH:33][CH:34]=2)[CH:25]=[C:26]([C:13]2[S:14][CH:15]=[CH:16][N:17]=2)[CH:27]=1)=[O:21]

Participants

9

Reactant 5

HCID 6325EthyleneHCID 6397ChlorotrimethylsilaneHCID 78391,2-DibromoethaneHCID 764302-BromothiazoleHCID 578515885-Iodo-4'-methyl-biphenyl-3-carboxylic acid methyl ester

Product 1

HCID 594325714'-Methyl-5-thiazol-2-yl-biphenyl-3-carboxylic acid methyl esterYield 80%

Reagents, catalysts & solvents 3

HCID 23994ZincCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8028TetrahydrofuranSolvent2×

Procedure

To a stirred suspension of zinc dust (3.06 g, 46.86 mmol) in THF (15 ml) was added 1,2-dibromoethane (0.327 ml, 3.83 mmol). The reaction mixture was heated until the evolution of ethylene was completed. Trimethylsilyl chloride (0.013 ml), THF (5 ml) and 2-bromothiazole (1.39 ml, 15.62 mmol) were added, and the reaction mixture was stirred for 20 minutes at room temperature. 5-Iodo-4′-methyl-biphenyl-3-carboxylic acid methyl ester (5.0 g, 14.2 mmol) and Pd(PPh3)4 (492.3 mg, 0.462 mmol) were added, and the mixture was refluxed for 14 hours. Th reaction mixture was cooled in an ice bath and extracted with EtOAc, washed with saturated aqueous NH4Cl, brine, dried over anhydrous Na2SO4, filtered, and concentrated in vacuo. The residue was purified by flash column chromatography on silica gel, eluting with hexanes-ethyl acetate (1:6), giving 4′-methyl-5-thiazol-2-yl-biphenyl-3-carboxylic acid methyl ester as a light yellow solid (0.42 g, 80%). MS (M+H)=310.

Workup

  1. temperaturethe mixture was refluxed for 14 hours
  2. temperatureTh reaction mixture was cooled in an ice bath
  3. extractionextracted with EtOAc
  4. washwashed with saturated aqueous NH4Cl, brine
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash column chromatography on silica gel
  9. washeluting with hexanes-ethyl acetate (1:6)

Sources & evidence

ORD record
ord-b0a74e33b7714e17830d8a1e5dab2a02
Source dataset
uspto-grants-2013_08
Patent number
US08501933B2

Reaction notes

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