Cesium carbonate → HCID 86695909, compound

HRID 870917Notes

Reaction equation

HRID 870917 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[C:3]=1[CH:16]=[O:17].[Cl:18][C:19]1[CH:24]=[CH:23][C:22](B(O)O)=[C:21]([F:28])[CH:20]=1.C(=O)([O-])[O-].[Cs+].[Cs+]>C1COCC1.O.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>[Cl:18][C:19]1[CH:24]=[CH:23][C:22]([C:2]2[CH:7]=[CH:6][N:5]=[C:4]([NH:8][C:9](=[O:15])[O:10][C:11]([CH3:14])([CH3:13])[CH3:12])[C:3]=2[CH:16]=[O:17])=[C:21]([F:28])[CH:20]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 4193595(4-Chloro-2-fluorophenyl)boronic acidHCID 86710339HCID 86710339, compound

Product 1

HCID 86695909HCID 86695909, compoundYield 51.5%

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 962WaterSolvent2×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
85 °C

Procedure

To a stirred suspension of tert-butyl (4-bromo-3-formylpyridin-2-yl)carbamate (100 mg, 0.332 mmol), (4-chloro-2-fluorophenyl)boronic acid (57.9 mg, 0.332 mmol) and cesium carbonate (216 mg, 0.664 mmol) in THF (50 mL) and water (8 ml) was added Pd(PPh3)4 (19.19 mg, 0.017 mmol) and the reaction mixture was heated to 85° C. overnight. The reaction mixture was cooled to room temperature, diluted with water (30 mL) and extracted with ethyl acetate (2×25 mL). The combined organic extracts were washed with brine (1×25 mL), dried over sodium sulfate and concentrated under reduced pressure. The crude residue was purified via silica gel chromatography (ethyl acetate/hexanes) to afford tert-butyl 4-(4-chloro-2-fluorophenyl)-3-formylpyridin-2-ylcarbamate (60 mg, 0.171 mmol, 35% yield). LCMS (ESI) m/e 349.2 [(M−H)−, calcd for C17H15ClFN2O3 349.1]; LC/MS retention time (Method C): tR=2.05 min.

Workup

  1. temperatureThe reaction mixture was cooled to room temperature
  2. extractionextracted with ethyl acetate (2×25 mL)
  3. washThe combined organic extracts were washed with brine (1×25 mL)
  4. dry with materialdried over sodium sulfate
  5. concentrationconcentrated under reduced pressure
  6. customThe crude residue was purified via silica gel chromatography (ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-7b5ca1b3341848fcbdd4ce5caa1d615f
Source dataset
uspto-grants-2015_03
Patent number
US08969564B2

Reaction notes

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