Dichloromethane → HCID 68183156, compound

HRID 1615516Notes

Reaction equation

HRID 1615516 reaction equation
Br[C:2]1[S:6][C:5]2[CH2:7][CH2:8][CH2:9][CH2:10][C:11](=[O:12])[C:4]=2[CH:3]=1.O1CCOCC1.[N:19]1[CH:24]=[CH:23][C:22](B(O)O)=[CH:21][CH:20]=1.C(=O)([O-])[O-].[Cs+].[Cs+].ClCCl>C(OCC)(=O)C.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[N:19]1[CH:24]=[CH:23][C:22]([C:2]2[S:6][C:5]3[CH2:7][CH2:8][CH2:9][CH2:10][C:11](=[O:12])[C:4]=3[CH:3]=2)=[CH:21][CH:20]=1

Participants

9

Reactant 5

HCID 6344DichloromethaneHCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 2734379(Pyridin-4-yl)boronic acidHCID 685259082-bromo-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophen-4-one

Product 1

HCID 68183156HCID 68183156, compoundYield 68%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
110 °C

Procedure

To a pressure tube were added 2-bromo-5,6,7,8-tetrahydro-4H-cyclohepta[b]thiophen-4-one (2.15 g, 8.77 mmol), 1,4-dioxane (54.8 mL, 702 mmol), pyridine-4-boronic acid (1.40 g, 11.4 mmol), cesium carbonate (8.50 g, 26.0 mmol), [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II), complex with dichloromethane (1:1) (380 mg, 0.460 mmol) and water (7.90 mL, 439 mmol). The tube was sealed and the mixture was heated at 110° C. for 16 hr. The reaction mixture was allowed to cool to rt then diluted with ethyl acetate (15 mL) and water (10 mL) and transferred to a separatory funnel. The organic layer was separated and the aqueous phase was extracted with ethyl acetate (3×10 mL). The combined organic phases were washed with brine (10 mL) then dried over anhydrous MgSO4. Insoluble materials were removed by filtration, the filtrate was concentrated and the obtained residue was purified by column chromatography (SiO2, elution with 0-100% EA/DCM) to give the title compound as a yellow foam (1.44 g, 68% yield). LCMS: (FA) ES+ , 244. 1H NMR (300 MHz, DMSO-d6) δ: 8.55-8.57 (dd, J=1.7 Hz, J=4.9 Hz, 2H), 7.91-7.92 (br s, 1H), 7.62-7.64 (dd, J=1.5 Hz, J=4.9 Hz, 2H), 3.15-3.20 (m, 2H), 2.69-2.73 (m, 2H), 1.80-1.90 (m, 4H).

Workup

  1. customThe tube was sealed
  2. temperatureto cool to rt
  3. customtransferred to a separatory funnel
  4. customThe organic layer was separated
  5. extractionthe aqueous phase was extracted with ethyl acetate (3×10 mL)
  6. washThe combined organic phases were washed with brine (10 mL)
  7. dry with materialthen dried over anhydrous MgSO4
  8. customInsoluble materials were removed by filtration
  9. concentrationthe filtrate was concentrated
  10. customthe obtained residue was purified by column chromatography (SiO2, elution with 0-100% EA/DCM)

Sources & evidence

ORD record
ord-2baba263b8004f15850c9aa9890cc45f
Source dataset
uspto-grants-2014_07
Patent number
US08765746B2

Reaction notes

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