Water → HCID 69673293, compound

HRID 1426301Notes

Reaction equation

HRID 1426301 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH:19]=[C:20]([F:22])[CH:21]=1)[O:5][CH:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2CCCCC2)C2C=CC=CC=2C2C(C(C)C)=CC(C(C)C)=CC=2C(C)C)CCCCC1.O>C1COCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:8][N:9]([CH2:12][C:2]1[CH:3]=[C:4]([CH:19]=[C:20]([F:22])[CH:21]=1)[O:5][CH:6]1[CH2:11][CH2:10][N:9]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH2:8][CH2:7]1)[CH3:10]

Participants

7

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 111557942-Dicyclohexylphosphino-2',4',6'-triisoprophylbiphenylHCID 69673392HCID 69673392, compound

Product 1

HCID 69673293HCID 69673293, compoundYield 178%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
80 °C

Procedure

To a microwave vial was added tert-butyl 4-(3-bromo-5-fluorophenoxy)piperidine-1-carboxylate (215 mg, 0.574 mmol), cesium carbonate (562 mg, 1.72 mmol), dicyclohexyl(2′,4′,6′-triisopropylbiphenyl-2-yl)phosphine (130 mg, 0.27 mmol), potassium [(dimethylamino)methyl](trifluoro)borate(1-) (114 mg, 0.689 mmol), palladium acetate (30.7 mg, 0.137 mmol) and 5.05M water in THF (3.5 mL). The tube was sealed and evacuated and refilled with N2 (3×). The sealed tube was then heated at 80° C. for 20 hours. The reaction was diluted with water and ethyl acetate. The aqueous layer was extracted with ethyl acetate once. The combined organic solutions were washed with brine, dried over Na2SO4, filtered and concentrated. The crude was purified with preparative LCMS (C18 column eluting with a gradient of ACN/H2O containing 0.1% TFA) to afford the desired product (180 mg, 89%). LCMS (M+H)+: 353.2.

Workup

  1. customThe tube was sealed
  2. customevacuated
  3. additionrefilled with N2 (3×)
  4. additionThe reaction was diluted with water and ethyl acetate
  5. extractionThe aqueous layer was extracted with ethyl acetate once
  6. washThe combined organic solutions were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude was purified with preparative LCMS (C18 column
  11. washeluting with a gradient of ACN/H2O containing 0.1% TFA)

Sources & evidence

ORD record
ord-654624c23b844f8fb6899168478d76c3
Source dataset
uspto-grants-2015_01
Patent number
US08933085B2

Reaction notes

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