Potassium Carbonate → 1186234-39-8

HRID 1469380Notes

Reaction equation

HRID 1469380 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5](B(O)O)=[CH:4][CH:3]=1.[N:11]1[CH:16]=[CH:15][CH:14]=[C:13]([NH:17][C:18]([N:20]2[CH2:23][CH:22]([O:24][C:25]3[CH:30]=[CH:29][C:28](I)=[CH:27][N:26]=3)[CH2:21]2)=[O:19])[N:12]=1.C(=O)([O-])[O-].[K+].[K+]>C1COCC1.O.C(OCC)(=O)C>[N:11]1[CH:16]=[CH:15][CH:14]=[C:13]([NH:17][C:18]([N:20]2[CH2:21][CH:22]([O:24][C:25]3[CH:30]=[CH:29][C:28]([C:3]4[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=4[F:1])=[CH:27][N:26]=3)[CH2:23]2)=[O:19])[N:12]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 2856454-Fluorophenylboronic acidHCID 66710496US10918640, Example 14

Product 1

HCID 442190541186234-39-8Yield 53.2%

Reagents, catalysts & solvents 2

HCID 8857Ethyl AcetateSolventHCID 21881883Oxolane--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

A solution of 4-fluorophenyl boronic acid (0.254 mg, 1.81 mmol) in THF/H2O (10:1; 10 mL) was added to a microwave vial containing 3-(5-iodo-pyridin-2-yloxy)-azetidine-1-carboxylic acid pyridazin-3-ylamide (Example 7, Step 1) (0.480 g, 1.21 mmol) and potassium carbonate (0.50 g, 3.63 mmol). Nitrogen gas was bubbled through the mixture for 5 mins then 1,1′-bis[(diphenylphosphino)-ferrocene]dichloropalladium(II) complex with CH2Cl2 (0.099 g, 10 mole %) was added and the vial sealed and heated at 100° C. in microwave synthesiser for 30 min. The cooled reaction mixture was diluted with ethyl acetate (20 mL) and washed sequentially with saturated aqueous sodium carbonate solution (20 mL) then saturated sodium chloride solution (20 mL). The mixture was dried over magnesium sulphate and filtered. Filtrate solvents were removed in vacuo to afford a brown gum, which was purified by flash chromatography, eluting with a gradient of 50% to 100% ethyl acetate in hexane to a afford a white solid (0.235 g, 53%)

Workup

  1. customNitrogen gas was bubbled through the mixture for 5 mins
  2. addition1,1′-bis[(diphenylphosphino)-ferrocene]dichloropalladium(II) complex with CH2Cl2 (0.099 g, 10 mole %) was added
  3. customthe vial sealed
  4. customThe cooled reaction mixture
  5. washwashed sequentially with saturated aqueous sodium carbonate solution (20 mL)
  6. dry with materialThe mixture was dried over magnesium sulphate
  7. filtrationfiltered
  8. customFiltrate solvents were removed in vacuo
  9. customto afford a brown gum, which
  10. customwas purified by flash chromatography
  11. washeluting with a gradient of 50% to 100% ethyl acetate in hexane to

Sources & evidence

ORD record
ord-6ff43132d5194623a40b5c8002cdcf66
Source dataset
uspto-grants-2015_04
Patent number
US09006269B2

Reaction notes

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