Cesium carbonate → HCID 46317762, compound

HRID 2401840Notes

Reaction equation

HRID 2401840 reaction equation
Br[C:2]1[S:6][C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:4][CH:3]=1.[N:12]1[CH:17]=[CH:16][C:15](B(O)O)=[CH:14][CH:13]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>O1CCOCC1.O.C(Cl)Cl.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>[N:12]1[CH:17]=[CH:16][C:15]([C:2]2[S:6][C:5]([C:7]([O:9][CH2:10][CH3:11])=[O:8])=[CH:4][CH:3]=2)=[CH:14][CH:13]=1

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 605723Ethyl 5-bromothiophene-2-carboxylateHCID 2734379(Pyridin-4-yl)boronic acid

Product 1

HCID 46317762HCID 46317762, compoundYield 66%

Reagents, catalysts & solvents 4

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of ethyl 5-bromothiophene-2-carboxylate (1.560 g, 6.65 mmol), pyridine-4-boronic acid (0.98 g, 7.98 mmol), tetrakis(triphenylphosphine)palladium(0) (768 mg, 0.665 mmol) and cesium carbonate (6.50 g, 19.9 mmol) in 1,4-dioxane (20 mL) and water (3.35 mL) was stirred and heated at 100° C. under an atmosphere of nitrogen overnight. The reaction was a clear light orange with a small amount of a second liquid phase on the bottom of the flask. An aliquot was taken, quenched into water, and extracted with ethyl acetate. A TLC on silica gel (1:1 DCM:hexane) indicated that all of the starting material had been consumed. A major new product with Rf ˜0.4 was seen. The reaction was cooled to room temperature then was quenched into stirring water and extracted with ethyl acetate. The ethyl acetate extracts were washed with saline, dried over sodium sulfate, filtered, and evaporated to leave crude product as an off-white solid. The crude product was dissolved in minimal DCM then was purified by column chromatography on silica gel (gradient 100% DCM to 50% ethyl acetate) to afford product 1.02 g (66% yield) as white solid. LC/MS (FA) ES+ 234. 1H NMR (400 MHz, DMSO) δ 8.68-8.60 (m, 2H), 7.91-7.83 (m, 2H), 7.78-7.71 (m, 2H), 4.37-4.27 (d, J=7.1 Hz, 2H), 1.35-1.27 (t, J=7.1 Hz, 3H).

Workup

  1. customquenched into water
  2. extractionextracted with ethyl acetate
  3. customhad been consumed
  4. temperatureThe reaction was cooled to room temperature
  5. customthen was quenched
  6. stirringinto stirring water
  7. extractionextracted with ethyl acetate
  8. washThe ethyl acetate extracts were washed with saline
  9. dry with materialdried over sodium sulfate
  10. filtrationfiltered
  11. customevaporated
  12. customto leave crude product as an off-white solid
  13. customthen was purified by column chromatography on silica gel (gradient 100% DCM to 50% ethyl acetate)

Sources & evidence

ORD record
ord-86ab2ca1a3e540efb02b63235536174a
Source dataset
uspto-grants-2014_08
Patent number
US08796268B2

Reaction notes

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