Hydrochloric Acid → HCID 59627927, compound

HRID 2421242Notes

Reaction equation

HRID 2421242 reaction equation
Br[C:2]1[CH:10]=[C:9]([F:11])[CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][N:6]2[C:12]1[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]2[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=2)=[C:14]([F:26])[CH:13]=1.[OH-:27].[K+].C(P(C(C)(C)C)C1C=CC=CC=1C1C(C(C)C)=CC(C(C)C)=CC=1C(C)C)(C)(C)C.Cl>O1CCOCC1.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]>[F:11][C:9]1[CH:10]=[C:2]([OH:27])[C:3]2[CH:4]=[CH:5][N:6]([C:12]3[CH:17]=[CH:16][C:15]([O:18][CH2:19][C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=4)=[C:14]([F:26])[CH:13]=3)[C:7]=2[CH:8]=1

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 14797Potassium HydroxideHCID 11618717Di-tert-butyl(2',4',6'-tris(propan-2-yl)-(1,1'-biphenyl)-2-yl)phosphaneHCID 66876830HCID 66876830, compound

Product 1

HCID 59627927HCID 59627927, compoundYield 46%

Reagents, catalysts & solvents 4

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
90 °C

Procedure

To a solution of 4-bromo-6-fluoro-1-{3-fluoro-4-[(phenylmethyl)oxy]phenyl}-1H-indole (D17) (980 mg, 2.366 mmol) in 1,4-dioxane (20 mL) and water (20 mL) was added potassium hydroxide (531 mg, 9.46 mmol). The reaction mixture was purged with argon and then treated with 2-di-tert-butylphosphino-2′,4′,6′-triisopropylbiphenyl (60.3 mg, 0.142 mmol) and tris(dibenzylideneacetone)dipalladium(0) (43.3 mg, 0.047 mmol). The reaction mixture was heated at 90° C. for 1 hour. After cooling to room temperature, the mixture was diluted with ethyl acetate and water. The pH was adjusted to ˜7 by the addition of 1M hydrochloric acid. After separation of the layers, the aqueous phase was re-extracted with ethyl acetate. The combined organic layers were dried over magnesium sulphate, filtered and concentrated. The product was purified by silica gel chromatography eluting with 5-40% ethyl acetate in hexane to yield the title compound (D18), (382 mg).

Workup

  1. customThe reaction mixture was purged with argon
  2. temperatureAfter cooling to room temperature
  3. customAfter separation of the layers
  4. extractionthe aqueous phase was re-extracted with ethyl acetate
  5. dry with materialThe combined organic layers were dried over magnesium sulphate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customThe product was purified by silica gel chromatography
  9. washeluting with 5-40% ethyl acetate in hexane

Sources & evidence

ORD record
ord-2d521ff3013c4080a39373aa3cb4fa1e
Source dataset
uspto-grants-2011_06
Patent number
US07956083B2

Reaction notes

Loading…