Cesium carbonate → 4-Chloro-3-cyclopropylpyridine

HRID 1480098Notes

Reaction equation

HRID 1480098 reaction equation
Br[C:2]1[CH:3]=[N:4][CH:5]=[CH:6][C:7]=1[Cl:8].[CH:9]1([B-](F)(F)F)[CH2:11][CH2:10]1.[K+].C(=O)([O-])[O-].[Cs+].[Cs+]>C1(C)C=CC=CC=1.O.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C(P(C12CC3CC(CC(C3)C1)C2)C12CC3CC(CC(C3)C1)C2)CCC>[Cl:8][C:7]1[CH:6]=[CH:5][N:4]=[CH:3][C:2]=1[CH:9]1[CH2:11][CH2:10]1

Participants

8

Reactant 3

HCID 10796Cesium carbonateHCID 8176963-Bromo-4-chloropyridineHCID 23697338Potassium cyclopropyltrifluoroborate

Product 1

HCID 713033264-Chloro-3-cyclopropylpyridineYield 75%

Reagents, catalysts & solvents 4

HCID 167845palladium(II) acetateCatalystHCID 11371790Bis(adamantan-1-yl)(butyl)phosphaneCatalystHCID 962WaterSolventHCID 1140TolueneSolvent

Conditions

Temperature
115 °C

Procedure

To a solution of 3-bromo-4-chloropyridine (CAN 36953-42-1, 4 g, 20.8 mmol) in a mixture of toluene (72 ml) and water (8.5 ml) under an argon atmosphere were added potassium cyclopropyltrifluoroborate (3.23 g, 21.8 mmol), palladium (II) acetate (93.3 mg, 416 μmol), butyldi-1-adamantylphosphine (224 mg, 624 μmol) and cesium carbonate (16.9 g, 52.0 mmol). The reaction mixture was stirred overnight at 115° C., cooled down to room temperature and filtered through a pad of celite. The filtrate was poured into a separatory funnel, diluted with ethyl acetate and extracted with an aqueous solution 1.0M sodium bicarbonate. The organic phase was collected, dried over sodium sulfate and evaporated down to dryness. The crude material was purified by flash chromatography on silica eluting with a heptane/(solution 3% triethylamine in ethyl acetate) gradient to yield the title product (2.39 g, 75%) as a yellow liquid. MS (ESI, m/z): 154.0 (M+H+).

Workup

  1. temperaturecooled down to room temperature
  2. filtrationfiltered through a pad of celite
  3. additionThe filtrate was poured into a separatory funnel
  4. additiondiluted with ethyl acetate
  5. extractionextracted with an aqueous solution 1.0M sodium bicarbonate
  6. customThe organic phase was collected
  7. dry with materialdried over sodium sulfate
  8. customevaporated down to dryness
  9. customThe crude material was purified by flash chromatography on silica eluting with a heptane/(solution 3% triethylamine in ethyl acetate) gradient

Sources & evidence

ORD record
ord-b1c548f67a4c4d1baa93d74c5462dd23
Source dataset
uspto-grants-2016_08
Patent number
US09409866B2

Reaction notes

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