Hydrogen Peroxide → HCID 67403888, compound

HRID 906172Notes

Reaction equation

HRID 906172 reaction equation
[C:1]([C:3]1[C:12](I)=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[C:5]([F:14])[CH:4]=1)#[N:2].C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:21][CH2:22][CH:23]([NH2:26])[CH2:24][CH3:25].CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)[O:48]C2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[K+].[K+].OO>CS(C)=O.C(OCC)(=O)C.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[NH2:2][C:1]([C:3]1[C:12]([NH:26][CH:23]([CH2:24][CH3:25])[CH2:22][CH3:21])=[CH:11][C:6]([C:7]([O:9][CH3:10])=[O:8])=[C:5]([F:14])[CH:4]=1)=[O:48]

Participants

11

Reactant 6

HCID 784Hydrogen PeroxideHCID 10796Cesium carbonateHCID 11430Potassium CarbonateHCID 120193-PentanamineHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 67404196Benzoic acid, 4-cyano-2-fluoro-5-iodo-, methyl ester

Product 1

HCID 67403888HCID 67403888, compoundYield 279.6%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

To a pressure vessel were added the above methyl 4-cyano-2-fluoro-5-iodobenzoate (˜0.93 mmol), cesium carbonate (606 mg, 1.86 mmol), pentan-3-amine (325 uL, 2.79 mmol), XANTPHOS (54 mg, 0.093 mmol), tris(dibenzylideneacetone)dipalladium(0) (43 mg, 0.047 mmol), and dioxane (4 mL). The vessel was sealed and heated to 95° C. for ˜17 h. After cooling to room temperature, the mixture was filtered through celite, and the filter cake rinsed with ethyl acetate. The filtrate was then concentrated. The residue was subject to column chromatography (10% ethyl acetate in hexanes). Eluent containing the desired project was collected and concentrated to afford an impure residue. This residue was dissolved in DMSO (6 mL) and was treated with potassium carbonate (111 mg, 0.8 mmol) and 30% aqueous hydrogen peroxide (150 uL). After stirring at room temperature for 30 min, the mixture was diluted with ethyl acetate. The organic solution was washed with a mixture of water and 10% aqueous lithium chloride. The aqueous wash was extracted with ethyl acetate. The combined organic extracts were washed with 10% aqueous lithium chloride, dried over magnesium sulfate, filtered, and concentrated. The residue was purified by gradient column chromatography (30% ethyl acetate in hexanes to 50% ethyl acetate in hexanes) to provide methyl 4-(aminocarbonyl)-2-fluoro-5-(pentan-3-ylamino)benzoate (73.7 mg, 0.26 mmol, 28% yield). 1H NMR (400 MHz, CDCl3): 7.42 (d, 1H), 7.18-7.15 (m, 2H), 5.86 (br s, 2H), 3.94 (s, 3H), 3.37-3.29 (m, 1H), 1.67-1.47 (m, 4H), 0.93 (t, 6H).

Workup

  1. customThe vessel was sealed
  2. temperatureAfter cooling to room temperature
  3. filtrationthe mixture was filtered through celite
  4. washthe filter cake rinsed with ethyl acetate
  5. concentrationThe filtrate was then concentrated
  6. additionEluent containing the desired project
  7. customwas collected
  8. concentrationconcentrated
  9. customto afford an impure residue
  10. washThe organic solution was washed with a mixture of water and 10% aqueous lithium chloride
  11. washThe aqueous wash
  12. extractionwas extracted with ethyl acetate
  13. washThe combined organic extracts were washed with 10% aqueous lithium chloride
  14. dry with materialdried over magnesium sulfate
  15. filtrationfiltered
  16. concentrationconcentrated
  17. customThe residue was purified by gradient column chromatography (30% ethyl acetate in hexanes to 50% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-8aea13fbfd4e439f9ffa21ca8a98fa4b
Source dataset
uspto-grants-2011_09
Patent number
US08012956B2

Reaction notes

Loading…