1-Bromo-4-tert-butylbenzene → Ethyl 4-[[4-(4-tert-butylphenyl)-2,2-dimethyl-(2H)-thiochromen-6-yl]-ethynyl]-benzoate

HRID 619624Notes

Reaction equation

HRID 619624 reaction equation
[C:1]([C:5]1[CH:10]=[CH:9][C:8](Br)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2].C([Li])(C)(C)C.[CH3:17][C:18]1([CH3:49])[CH:27]=[C:26](OS(C(F)(F)F)(=O)=O)[C:25]2[C:20](=[CH:21][CH:22]=[C:23]([C:36]#[C:37][C:38]3[CH:48]=[CH:47][C:41]([C:42]([O:44][CH2:45][CH3:46])=[O:43])=[CH:40][CH:39]=3)[CH:24]=2)[S:19]1>C1COCC1.CCCCC.[Cl-].[Cl-].[Zn+2].[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[C:1]([C:5]1[CH:10]=[CH:9][C:8]([C:26]2[C:25]3[C:20](=[CH:21][CH:22]=[C:23]([C:36]#[C:37][C:38]4[CH:48]=[CH:47][C:41]([C:42]([O:44][CH2:45][CH3:46])=[O:43])=[CH:40][CH:39]=4)[CH:24]=3)[S:19][C:18]([CH3:17])([CH3:49])[CH:27]=2)=[CH:7][CH:6]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

8

Reactant 3

HCID 775951-Bromo-4-tert-butylbenzeneHCID 10051511ethyl 4-(2,2-dimethyl-4-trifluoromethanesulfonyloxy-(2H)-thio-chromen-6-ylethynyl)-benzoate2×HCID 178418306HCID 178418306, compound

Product 1

HCID 21846671Ethyl 4-[[4-(4-tert-butylphenyl)-2,2-dimethyl-(2H)-thiochromen-6-yl]-ethynyl]-benzoate

Reagents, catalysts & solvents 4

HCID 3007855ZincchlorideCatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8003PentaneSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of 4-tert-butylbromobenzene (149.0 mg, 0.70 mmol) in 2.0 mL of THF was cooled to -78° C. and tert-butyllithium (92.6 mg, 1.44 mmol, 0.85 ml of a 1.7M solution in pentane) was added to give a yellow solution. After 30 minutes a solution of ZnCl2 (133.0 mg, 0.98 mmol) in 4.0 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)-thiochromen-6-ylethynyl) benzoate (Compound 224, 140.0 mg, 0.28 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. The 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, 94.0 mg (70%), was isolated by column chromatography (5% EtOAc/hexanes) as a colorless solid. 1H NMR (300 MHz, CDCl3) δ: 7.98 (2H, d, J=8.3 Hz), 7.52 (2H, d, J=8.3 Hz), 7.43-7.22 (7H, m), 5.86 (1H, s), 4.38 (2H, q, J=7.1 Hz), 1.47 (6H, s), 1.40 (3H, t, J=7.1 Hz), 1.38 (9H, s).

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. extractionThe 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-82c06b0e6b584a33b9b008781e089000
Source dataset
uspto-grants-1999_09
Patent number
US05958954

Reaction notes

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