Cesium carbonate → HCID 86695909, compound

HRID 1398342Notes

Reaction equation

HRID 1398342 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 51.2%

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 (14 h). 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, 0.17 mmol, 35% yield). LC/MS (ESI) m/e 351.2 [(M+H)+, calcd for C17H17ClFN2O3351.1]. LC/MS retention time (method A): tR=2.07 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-591e0bbd16044be38302a6d6e71dee02
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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