2-Methylthiophene → HCID 21846701, compound

HRID 619625Notes

Reaction equation

HRID 619625 reaction equation
[CH3:1][C:2]1[S:3][CH:4]=[CH:5][CH:6]=1.C([Li])CCC.[CH3:12][C:13]1([CH3:44])[CH:22]=[C:21](OS(C(F)(F)F)(=O)=O)[C:20]2[C:15](=[CH:16][CH:17]=[C:18]([C:31]#[C:32][C:33]3[CH:43]=[CH:42][C:36]([C:37]([O:39][CH2:40][CH3:41])=[O:38])=[CH:35][CH:34]=3)[CH:19]=2)[S:14]1>C1COCC1.[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>[CH3:1][C:2]1[S:3][C:4]([C:21]2[C:20]3[C:15](=[CH:16][CH:17]=[C:18]([C:31]#[C:32][C:33]4[CH:43]=[CH:42][C:36]([C:37]([O:39][CH2:40][CH3:41])=[O:38])=[CH:35][CH:34]=4)[CH:19]=3)[S:14][C:13]([CH3:12])([CH3:44])[CH:22]=2)=[CH:5][CH:6]=1

Participants

7

Reactant 3

HCID 111262-MethylthiopheneHCID 10051511ethyl 4-(2,2-dimethyl-4-trifluoromethanesulfonyloxy-(2H)-thio-chromen-6-ylethynyl)-benzoate2×HCID 178418339Butyllithium

Product 1

HCID 21846701HCID 21846701, compound

Reagents, catalysts & solvents 3

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

Conditions

Temperature
0 °C

Procedure

A solution of 2-methylthiophene (100.0 mg, 1.00 mmol) in 2.0 mL of THF was cooled to -78° C. and n-butyllithium (64.0 mg, 1.00 mmol, 0.63 ml of a 1.6M solution in hexanes) was added and the solution warmed to 0° C. during 1.5 hours. A solution of ZnCl2 (218.0 mg, 1.60 mmol) in 3.0 mL THF was slowly added via cannula. The resulting solution was warmed to room temperature, stirred for 40 minutes, and transferred via cannula to a solution of ethyl 4-[(2,2-dimethyl-4-trifluoromethanesulfonyloxy-(2H)-thiochromen-6-yl)ethynyl]-benzoate (Compound 224, 200.0 mg, 0.40 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, 170.0 mg (96%), was isolated by column chromatography (5% EtOAc/hexanes) as a pale-yellow solid. 1H NMR (300 MHz, CDCl3) δ: 8.01 (2H, d, J=8.3 Hz), 7.63 (1H, s), 7.55 (2H, d, J=8.3 Hz), 7.35 (2H, s), 6.82 (1H, d, J=3.5 Hz), 6.72 (1H, m), 6.00 (1H, s), 4.38 (2H, q, J=7.1 Hz), 2.52 (3H, s), 1.46 (6H, s), 1.40 (2H, t, J=7.1 Hz).

Workup

  1. temperatureThe resulting solution was warmed to room temperature
  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-cae0346969584d0593464654e93b0e58
Source dataset
uspto-grants-1999_09
Patent number
US05958954

Reaction notes

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