Potassium Carbonate → Tert-butyl {1-[5-chloro-3-(5-fluoropyridin-3-yl)-2-methoxy-4-methylphenyl]propyl}carbamate

HRID 510985Notes

Reaction equation

HRID 510985 reaction equation
Br[C:2]1[C:3]([O:21][CH3:22])=[C:4]([CH:10]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH2:11][CH3:12])[CH:5]=[C:6]([Cl:9])[C:7]=1[CH3:8].[F:23][C:24]1[CH:25]=[N:26][CH:27]=[C:28](B2OC(C)(C)C(C)(C)O2)[CH:29]=1.C(=O)([O-])[O-].[K+].[K+]>O1CCOCC1.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:9][C:6]1[C:7]([CH3:8])=[C:2]([C:28]2[CH:27]=[N:26][CH:25]=[C:24]([F:23])[CH:29]=2)[C:3]([O:21][CH3:22])=[C:4]([CH:10]([NH:13][C:14](=[O:20])[O:15][C:16]([CH3:19])([CH3:18])[CH3:17])[CH2:11][CH3:12])[CH:5]=1

Participants

7

Reactant 3

HCID 11430Potassium CarbonateHCID 164142683-Fluoro-5-(tetramethyl-1,3,2-dioxaborolan-2-yl)pyridineHCID 88540645Tert-butyl[1-(3-bromo-5-chloro-2-methoxy-4-methylphenyl)propyl]carbamate

Product 1

HCID 86666900Tert-butyl {1-[5-chloro-3-(5-fluoropyridin-3-yl)-2-methoxy-4-methylphenyl]propyl}carbamateYield 77%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
90 °C

Procedure

The tert-butyl [1-(3-bromo-5-chloro-2-methoxy-4-methylphenyl)propyl]carbamate peak 2 (0.075 g, 0.19 mmol) was combined with 3-fluoro-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (0.081 g, 0.29 mmol, Frontier Scientific, catalog #F2018) in 1,4-dioxane (4.6 mL) and potassium carbonate (0.053 g, 0.38 mmol) in water (1.5 mL) in a tube. This was degassed with nitrogen and the tetrakis(triphenylphosphine)palladium(0) (0.02 g, 0.02 mmol) was added. The reaction was degassed with nitrogen, sealed and heated to 90° C. in an oil bath. The reaction was complete after 18 h, and the reaction mixture was allowed to cool and partitioned between EtOAc and water. The organic layer was washed with brine, dried over magnesium sulfate and concentrated to give the crude product as an oil. The product was purified by chromatography on silica gel eluting with a hexane:EtOAc gradient to give tert-butyl {1-[5-chloro-3-(5-fluoropyridin-3-yl)-2-methoxy-4-methylphenyl]propyl}carbamate as a viscous oil (0.05 g, 77%). LCMS calculated for C21H27ClFN2O3 (M+H)+: m/z=409.1. found: 409.1.

Workup

  1. customThis was degassed with nitrogen
  2. customThe reaction was degassed with nitrogen
  3. customsealed
  4. temperatureto cool
  5. custompartitioned between EtOAc and water
  6. washThe organic layer was washed with brine
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated
  9. customto give the crude product as an oil
  10. customThe product was purified by chromatography on silica gel eluting with a hexane

Sources & evidence

ORD record
ord-38429a9892754a228cf01455b0010639
Source dataset
uspto-grants-2015_08
Patent number
US09096600B2

Reaction notes

Loading…