4-Bromotoluene → HCID 21846645, compound

HRID 619651Notes

Reaction equation

HRID 619651 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5](Br)=[CH:4][CH:3]=1.C([Li])(C)(C)C.[CH3:14][C:15]1([CH3:46])[CH:24]=[C:23](OS(C(F)(F)F)(=O)=O)[C:22]2[C:17](=[CH:18][CH:19]=[C:20]([C:33]#[C:34][C:35]3[CH:45]=[CH:44][C:38]([C:39]([O:41][CH2:42][CH3:43])=[O:40])=[CH:37][CH:36]=3)[CH:21]=2)[O:16]1>C1COCC1.CCCCC.[Cl-].[Cl-].[Zn+2].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>[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([C:23]2[C:22]3[C:17](=[CH:18][CH:19]=[C:20]([C:33]#[C:34][C:35]4[CH:45]=[CH:44][C:38]([C:39]([O:41][CH2:42][CH3:43])=[O:40])=[CH:37][CH:36]=4)[CH:21]=3)[O:16][C:15]([CH3:14])([CH3:46])[CH:24]=2)=[CH:4][CH:3]=1

Participants

8

Reactant 3

HCID 78054-BromotolueneHCID 21846667HCID 21846667, compound2×HCID 178418306HCID 178418306, compound

Product 1

HCID 21846645HCID 21846645, compound

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 178418397HCID 178418397, compoundCatalystHCID 8003PentaneSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of 4-methylbromobenzene (237.0 mg, 1.38 mmol) in 3.0 mL of THF was cooled to -78° C. and tert-butyllithium (177.5 mg, 2.77 mmol, 1.6 ml of a 1.7M solution in pentane) was added to give a yellow solution. After 30 minutes a solution of ZnCl2 (377.0 mg, 2.77 mmol) in 5.0 mL THF was slowly added via cannula. The resulting solution was warmed to room temperature and transferred via cannula to a solution of ethyl 4-(2,2-dimethyl-4-trifluoromethanesulfonyloxy-(2H)-chromen-6-ylethynyl)-benzoate (Compound 264, 150.0 mg, 0.31 mmol) and tetrakis(triphenylphosphine)palladium(0) (24.0 mg, 0.02 mmol) in 2.0 mL THF. This solution was heated to 50° C. for 2 hours, cooled to room temperature, and the reaction quenched by the addition of saturated aqueous NH4Cl. This solution was extracted with EtOAc and the combined organic layers were washed with H2O and saturated aqueous NaCl before being dried (MgSO4) and concentrated under reduced pressure. The title compound, 120.0 mg (92%), was isolated by column chromatography (2.5% EtOAc/hexanes) as a colorless solid. 1H NMR (300 MHz, CDCl3) δ: 7.98 (2H, d, J=8.5 Hz), 7.50 (2H, d, J=8.5 Hz), 7.34 (1H, dd, J=2.1, 8.3 Hz), 7.25-7.21 (5H, m), 6.85 (1H, d, J=8.3 Hz), 5.62 (1H, s), 4.36 (2H, q, J=7.1 Hz), 2.41 (3H, s), 1.49 (6H, s), 1.39 (3H, t, J=7.1 Hz).

Workup

  1. customto give a yellow solution
  2. temperatureThis solution was heated to 50° C. for 2 hours
  3. temperaturecooled to room temperature
  4. customthe reaction quenched by the addition of saturated aqueous NH4Cl
  5. extractionThis solution was extracted with EtOAc
  6. washthe combined organic layers were washed with H2O and saturated aqueous NaCl
  7. dry with materialbefore being dried (MgSO4)
  8. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-a1279b369f4944eaa6a9b8d25e4566dc
Source dataset
uspto-grants-1999_09
Patent number
US05958954

Reaction notes

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