1-Bromo-4-ethylbenzene → HCID 21846673, compound

HRID 619632Notes

Reaction equation

HRID 619632 reaction equation
[CH2:1]([C:3]1[CH:8]=[CH:7][C:6](Br)=[CH:5][CH:4]=1)[CH3:2].C([Li])(C)(C)C.[CH3:15][C:16]1([CH3:47])[CH:25]=[C:24](OS(C(F)(F)F)(=O)=O)[C:23]2[C:18](=[CH:19][CH:20]=[C:21]([C:34]#[C:35][C:36]3[CH:46]=[CH:45][C:39]([C:40]([O:42][CH2:43][CH3:44])=[O:41])=[CH:38][N:37]=3)[CH:22]=2)[S:17]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>[CH2:1]([C:3]1[CH:8]=[CH:7][C:6]([C:24]2[C:23]3[C:18](=[CH:19][CH:20]=[C:21]([C:34]#[C:35][C:36]4[CH:46]=[CH:45][C:39]([C:40]([O:42][CH2:43][CH3:44])=[O:41])=[CH:38][N:37]=4)[CH:22]=3)[S:17][C:16]([CH3:15])([CH3:47])[CH:25]=2)=[CH:5][CH:4]=1)[CH3:2]

Participants

8

Reactant 3

HCID 153131-Bromo-4-ethylbenzeneHCID 21846670HCID 21846670, compound2×HCID 178418306HCID 178418306, compound

Product 1

HCID 21846673HCID 21846673, compound

Reagents, catalysts & solvents 4

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

Procedure

A solution of 4-ethylbromobenzene (300.0 mg, 1.62 mmol) in 2.0 mL of THF was cooled to -78° C. and tert-butyllithium (207.6 mg, 3.24 mmol, 1.9 mL of a 1.7M solution in pentane) was added to give a yellow solution. After 30 minutes a solution of ZnCl2 (408.0 mg, 3.0 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 6-(2,2-dimethyl-4-trifluoromethanesulfonyloxy-(2H)-thiochromen-6-ylethynyl) nicotinate (Compound 239, 178.0 mg, 0.36 mmol) and tetrakis(triphenylphosphine)palladium(0) (24 mg, 0.02 mmol) in 2.0 mL THF. This solution was heated to 50° C. for 1 hour, 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 was isolated by column chromatography (10 to 15% EtOAc/hexanes) and recrystalization from CH3CN to give 136.0 mg (83%) of pale yellow crystals. 1H NMR (300 MHz, CDCl3) δ: 9.15 (1H, s), 8.23 (1H, dd, J=2.2, 8.2 Hz), 7.51 (1H, d, J=8.1 Hz), 7.49-7.34 (3H, m), 7.24-7.17 (4H, m), 5.83 (1H, s), 4.40 (2H, q, J=7.1 Hz), 2.70 (2H, q, J=7.6 Hz), 1.47 (6H, s), 1.40 (3H, t, J=7.1 Hz), 1.29 (3H, t, J=7.1 Hz).

Workup

  1. customto give a yellow solution
  2. temperatureThis solution was heated to 50° C. for 1 hour
  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-0b353fa38b0044059ddf7313344c60ea
Source dataset
uspto-grants-1999_09
Patent number
US05958954

Reaction notes

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