Potassium Acetate → Ethyl 1-(3-fluoro-4-(5-(pyridin-2-ylmethyl)benzofuran-2-yl)benzyl)azetidine-3-carboxylate

HRID 2075204Notes

Reaction equation

HRID 2075204 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][C:8]1[CH:9]=[CH:10][C:11]2[O:15][C:14](B(O)O)=[CH:13][C:12]=2[CH:19]=1.C([O-])(=O)C.[K+].Br[C:26]1[CH:41]=[CH:40][C:29]([CH2:30][N:31]2[CH2:34][CH:33]([C:35]([O:37][CH2:38][CH3:39])=[O:36])[CH2:32]2)=[CH:28][C:27]=1[F:42]>CCO>[F:42][C:27]1[CH:28]=[C:29]([CH2:30][N:31]2[CH2:34][CH:33]([C:35]([O:37][CH2:38][CH3:39])=[O:36])[CH2:32]2)[CH:40]=[CH:41][C:26]=1[C:14]1[O:15][C:11]2[CH:10]=[CH:9][C:8]([CH2:7][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)=[CH:19][C:12]=2[CH:13]=1

Participants

5

Reactant 3

HCID 517044Potassium AcetateHCID 584152775-(Pyridin-2-ylmethyl)benzofuran-2-ylboronic acidHCID 58415312Ethyl 1-(4-bromo-3-fluorobenzyl)azetidine-3-carboxylate

Product 1

HCID 58415388Ethyl 1-(3-fluoro-4-(5-(pyridin-2-ylmethyl)benzofuran-2-yl)benzyl)azetidine-3-carboxylate

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

In a sealed flask, a mixture of 5-(pyridin-2-ylmethyl)benzofuran-2-ylboronic acid (214 mg, 846 μmol) and potassium acetate (166 mg, 1691 μmol) was set under argon, treated with bis{di(tbutyl)phenyl}palladium(II) dichloride (32 mg, 51 μmol), followed by a solution of ethyl 1-(4-bromo-3-fluorobenzyl)azetidine-3-carboxylate (267 mg, 846 μmol) in EtOH (5 mL). The resulting suspension was degassed again and heated to 80° C. for 2.5 h. The mixture was cooled to ˜10° C. and dropwise treated with H2O (15 mL). The mixture was extracted 2× with EtOAc. The combined organic layers were dried over MgSO4 and evaporated. Purification by flash chromatography (DCM to DCM/MeOH=4:1) gave ethyl 1-((3-fluoro-4-(5-(pyridin-2-ylmethyl)benzofuran-2-yl)phenyl)methyl)azetidine-3-carboxylate as a yellow foam.

Workup

  1. customThe resulting suspension was degassed again
  2. temperatureThe mixture was cooled to ˜10° C.
  3. additiondropwise treated with H2O (15 mL)
  4. extractionThe mixture was extracted 2× with EtOAc
  5. dry with materialThe combined organic layers were dried over MgSO4
  6. customevaporated
  7. customPurification by flash chromatography (DCM to DCM/MeOH=4:1)

Sources & evidence

ORD record
ord-25e570b33dd842729abf47b41be0c8ff
Source dataset
uspto-grants-2011_04
Patent number
US07919519B2

Reaction notes

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