Sodium Carbonate → (RS)-N-(4-cyano-benzyl)-2-(2,6-difluoro-3-pyridin-2-yl-phenyl)-2-ethoxy-acetamide

HRID 1247388Notes

Reaction equation

HRID 1247388 reaction equation
[C:1]([C:3]1[CH:32]=[CH:31][C:6]([CH2:7][NH:8][C:9]([CH:11]([O:28][CH2:29][CH3:30])[C:12]2[C:13]([F:27])=[C:14](OS(C(F)(F)F)(=O)=O)[CH:15]=[CH:16][C:17]=2[F:18])=[O:10])=[CH:5][CH:4]=1)#[N:2].B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.CC([O-])=O.[K+].Br[C:57]1[CH:58]=[CH:59][CH:60]=[N:61][CH:62]=1.C([O-])([O-])=O.[Na+].[Na+]>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[C:1]([C:3]1[CH:32]=[CH:31][C:6]([CH2:7][NH:8][C:9](=[O:10])[CH:11]([C:12]2[C:17]([F:18])=[CH:16][CH:15]=[C:14]([C:60]3[CH:59]=[CH:58][CH:57]=[CH:62][N:61]=3)[C:13]=2[F:27])[O:28][CH2:29][CH3:30])=[CH:5][CH:4]=1)#[N:2]

Participants

8

Reactant 5

HCID 10340Sodium CarbonateHCID 122863-BromopyridineHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 86593051(RS)-trifluoro-methanesulfonic acid 3-[(4-cyano-benzylcarbamoyl)-ethoxy-methyl]-2,4-difluoro-phenyl ester

Product 1

HCID 21905316(RS)-N-(4-cyano-benzyl)-2-(2,6-difluoro-3-pyridin-2-yl-phenyl)-2-ethoxy-acetamideYield 65%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalyst2×HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of (RS)-trifluoro-methanesulfonic acid 3-[(4-cyano-benzylcarbamoyl)-ethoxy-methyl]-2,4-difluoro-phenyl ester (570 mg) in dioxane (20 ml) was added bis(pinacolato)diboron (454 mg), dry KOAc (351 mg) and [PdCl2(PPh3)2] (25 mg). The reaction mixture was stirred 24 h at 100° C. After cooling to rt 5-bromopyridine (377 mg), 2 N aq. Na2CO3 sol. (6 ml) and [PdCl2(PPh3)2] (25 mg) were added. The resulting mixture was stirred 1 h at 90° C. The solids were filtered away and washed with H2O (100 ml) and AcOEt (80 ml). The aqueous layer was isolated and extracted with more AcOEt (100 ml). The organic layers were washed with brine (2×80 ml), combined and dried over Na2SO4. The solvent was evaporated and the crude product was purified by CC (AcOEt/Hept 3:7 to 3:1) to obtain 315 mg (65%) of (RS)-N-(4-cyano-benzyl)-2-(2,6-difluoro-3-pyridin-2-yl-phenyl)-2-ethoxy-acetamide. Colorless oil. MS 408.3 ([M+H]+).

Workup

  1. additionwere added
  2. stirringThe resulting mixture was stirred 1 h at 90° C
  3. filtrationThe solids were filtered away
  4. washwashed with H2O (100 ml) and AcOEt (80 ml)
  5. customThe aqueous layer was isolated
  6. extractionextracted with more AcOEt (100 ml)
  7. washThe organic layers were washed with brine (2×80 ml)
  8. dry with materialdried over Na2SO4
  9. customThe solvent was evaporated
  10. customthe crude product was purified by CC (AcOEt/Hept 3:7 to 3:1)

Sources & evidence

ORD record
ord-933fbf5690324eb0a36ba70a715cf670
Source dataset
uspto-grants-2006_10
Patent number
US07129238B2

Reaction notes

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