Water → ethyl 3-bromo-4-cyano-5-(3,6-dihydro-2H-pyran-4-yl)thiophene-2-carboxylate

HRID 2402111Notes

Reaction equation

HRID 2402111 reaction equation
[Br:1][C:2]1[C:6]([C:7]#[N:8])=[C:5](Br)[S:4][C:3]=1[C:10]([O:12][CH2:13][CH3:14])=[O:11].[O:15]1[CH2:20][CH:19]=[C:18](B2OC(C)(C)C(C)(C)O2)[CH2:17][CH2:16]1.O1CCOCC1.O.C(=O)([O-])[O-].[Cs+].[Cs+]>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>[Br:1][C:2]1[C:6]([C:7]#[N:8])=[C:5]([C:18]2[CH2:19][CH2:20][O:15][CH2:16][CH:17]=2)[S:4][C:3]=1[C:10]([O:12][CH2:13][CH3:14])=[O:11]

Participants

7

Reactant 5

HCID 962WaterHCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 112180533,6-Dihydro-2H-pyran-4-boronic acid pinacol esterHCID 66747477Ethyl 3,5-dibromo-4-cyanothiophene-2-carboxylate

Product 1

HCID 66747715ethyl 3-bromo-4-cyano-5-(3,6-dihydro-2H-pyran-4-yl)thiophene-2-carboxylateYield 63%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Conditions

Temperature
100 °C

Procedure

To a microwave vial containing a suspension of ethyl 3,5-dibromo-4-cyanothiophene-2-carboxylate (300.0 mg, 0.8849 mmol, prepared as in MPI10-008P1M) and 3,6-dihydro-2h-pyran-4-boronic acid pinacol ester (204 mg, 0.973 mmol) in 1,4-dioxane (8.98 mL, 115 mmol) and water (0.925 mL, 51.3 mmol) were added tetrakis(triphenylphosphine)palladium(0) (102 mg, 0.0885 mmol) and cesium carbonate (865 mg, 2.65 mmol). The vial was sealed, degassed by bubbling argon through for 10 minutes, and then heated at 100° C. with stirring for 24 h. The reaction was then cooled to room temperature and partitioned between EtOAc and water. Layers were separated, and, the aqueous layer was extracted 2× with EtOAc. Combined organic layers were dried over Na2SO4, filtered, and concentrated in vacuo. Residue was subjected to column chromatography as a solution in DCM (40 g column, gradient elution 0 to 25% EtOAc/hexanes) to afford ethyl 3-bromo-4-cyano-5-(3,6-dihydro-2H-pyran-4-yl)thiophene-2-carboxylate as a white solid (183 mg, yield 63%). LCMS: (FA) ES+ 342, 344; 1H NMR (400 MHz, DMSO) δ 6.86-6.79 (m, 1H), 4.36-4.27 (m, 4H), 3.82 (dd, J=5.4, 5.4, 2H), 2.53 (ddd, J=2.1, 4.9, 10.0, 2H), 1.30 (dd, J=7.1, 7.1, 3H).

Workup

  1. additionTo a microwave vial containing
  2. customThe vial was sealed
  3. customdegassed
  4. customby bubbling argon through for 10 minutes
  5. temperatureThe reaction was then cooled to room temperature
  6. custompartitioned between EtOAc and water
  7. customLayers were separated
  8. extractionthe aqueous layer was extracted 2× with EtOAc
  9. dry with materialCombined organic layers were dried over Na2SO4
  10. filtrationfiltered
  11. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-48e9f277f2944563bd5c1d0fcb3261a4
Source dataset
uspto-grants-2014_08
Patent number
US08796271B2

Reaction notes

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