Acetic Acid → 3-{[(Benzyloxy)carbonyl]amino}-7-vinylquinoline-2-carboxylic acid

HRID 924417Notes

Reaction equation

HRID 924417 reaction equation
[CH2:1]([O:8][C:9]([NH:11][C:12]1[C:13]([C:23]([O:25]CC)=[O:24])=[N:14][C:15]2[C:20]([CH:21]=1)=[CH:19][CH:18]=[C:17](Br)[CH:16]=2)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].[CH:36](B1OC(C)(C)C(C)(C)O1)=[CH2:37].CC(O)=O>O1CCOCC1.CC(C1C=C(C(C)C)C(C2C=CC=C(P(C3CCCCC3)C3CCCCC3)C=2)=C(C(C)C)C=1)C.C1C=[C-]C(C2C(N)=CC=CC=2)=CC=1.Cl[Pd+]>[CH2:1]([O:8][C:9]([NH:11][C:12]1[C:13]([C:23]([OH:25])=[O:24])=[N:14][C:15]2[C:20]([CH:21]=1)=[CH:19][CH:18]=[C:17]([CH:36]=[CH2:37])[CH:16]=2)=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 176Acetic AcidHCID 62657Potassium Phosphate, TribasicHCID 52330122-Ethenyl-4,4,5,5-tetramethyl-1,3,2-dioxaborolaneHCID 86726857Ethyl 3-(((benzyloxy)carbonyl)amino)-7-bromoquinoline-2-carboxylate

Product 1

HCID 867268683-{[(Benzyloxy)carbonyl]amino}-7-vinylquinoline-2-carboxylic acidYield 85.5%

Reagents, catalysts & solvents 2

HCID 72376365[2-(2-Aminophenyl)phenyl]-chloro-palladium dicyclohexyl-[3-(2,4,6-triisopropylphenyl)phenyl]phosphaneCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a screw-cap vial equipped with a magnetic stir bar, ethyl 3-{[(benzyloxy)carbonyl]amino}-7-bromoquinoline-2-carboxylate (Example 1, step 3, 971.6 mg, 2.263 mmol), chloro(2-dicyclohexylphosphino-2′,4′,6′-triisopropyl-1,1′-biphenyl) [2-(2′-amino-1,1′-biphenyl)]palladium(II) (Aldrich, 163.8 mg, 0.2082 mmol) and K3PO4 (1017.1 mg, 4.7916 mmol) were added. The vial was sealed with a Teflon-lined septum, evacuated and backfilled with nitrogen (this process was repeated a total of three times). A solution of vinylboronic acid pinacol ester (561.6 mg, 3.646 mmol) in 1,4-dioxane (10.0 mL) was added via a syringe, followed by deoxygenated water (8.0 mL). The mixture was then heated at 90° C. for 6 h. After the reaction was cooled to room temperature, water (50 mL) was added. AcOH (1.50 mL, 26.4 mmol) was added to adjust the pH to 5. The mixture was extracted with EtOAc (3×50 mL). The combined organic layer was washed with brine (100 mL), dried over Na2SO4 and concentrated under reduced pressure. The resulting residue was purified by flash chromatography on silica gel (0-10% MeOH in DCM) to give the title compound as a yellow solid (673.9 mg, 85%). LCMS calc. for C20H17N2O4 (M+H)+: m/z=349.1. found 349.1.

Workup

  1. customTo a screw-cap vial equipped with a magnetic stir bar
  2. customevacuated
  3. customby deoxygenated water (8.0 mL)
  4. temperatureAfter the reaction was cooled to room temperature
  5. additionwater (50 mL) was added
  6. extractionThe mixture was extracted with EtOAc (3×50 mL)
  7. washThe combined organic layer was washed with brine (100 mL)
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated under reduced pressure
  10. customThe resulting residue was purified by flash chromatography on silica gel (0-10% MeOH in DCM)

Sources & evidence

ORD record
ord-2ab5288b22f848109ea87d8fcc941d57
Source dataset
uspto-grants-2016_03
Patent number
US09278950B2

Reaction notes

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