Potassium Phosphate, Tribasic → HCID 86698779, compound

HRID 1054791Notes

Reaction equation

HRID 1054791 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][C:10]=1[Cl:11])[N:7]([C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])[CH:6]=[C:5]2[C:19]([O:21][CH3:22])=[O:20].CC1(C)C(C)(C)OB([C:31]2[CH:36]=[CH:35][C:34]([OH:37])=[CH:33][CH:32]=2)O1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2].O1CCOCC1>[Cl:11][C:10]1[CH:9]=[C:8]2[C:4]([C:5]([C:19]([O:21][CH3:22])=[O:20])=[CH:6][N:7]2[C:12]([O:14][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:13])=[CH:3][C:2]=1[C:31]1[CH:36]=[CH:35][C:34]([OH:37])=[CH:33][CH:32]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27346244-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)phenolHCID 86698780HCID 86698780, compound

Product 1

HCID 86698779HCID 86698779, compoundYield 89%

Reagents, catalysts & solvents 2

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
85 °C

Procedure

A mixture of 1-tert-butyl 3-methyl 5-bromo-6-chloro-1H-indole-1,3-dicarboxylate (300 mg, 0.78 mmol), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenol (255 mg, 1.16 mmol), 1,4-dioxane (4.2 mL) and aqueous potassium phosphate tribasic (4.6 mL, 0.5 M, 2.3 mmol) was treated with [1,1′-bis(diphenylphosphino)ferrocene]dichloropalladium(II) (57 mg, 0.78 mmol). The pink mixture was evacuated and refilled with nitrogen three times. The sealed reaction was heated at 85° C. for 10 minutes. The cooled reaction mixture was filtered through Celite, and the filter pad was washed with water followed by three washes with ethyl acetate. The filtrate layers were separated, and the aqueous layer was extracted again with ethyl acetate. The organic extracts were combined, washed with brine and then dried over sodium sulfate. The mixture was filtered and concentrated in vacuo to give an oily solid which was purified by flash chromatography eluting with heptanes/ethyl acetate (90:10 to 40:60) to give the title compound (279 mg, 89% yield) as a white solid. MS (ES+) 302 (M-Boc+1)+. 1H NMR (500 MHz, DMSO-d6) δ 9.62 (s, 1H), 8.26 (s, 1H), 8.21 (s, 1H), 7.95 (s, 1H), 7.26 (d, J=8.29 Hz, 2H), 6.86 (d, J=8.54 Hz, 2H), 3.32 (s, 3H), 1.66 (s, 9H).

Workup

  1. customThe pink mixture was evacuated
  2. additionrefilled with nitrogen three times
  3. customThe sealed reaction
  4. customThe cooled reaction mixture
  5. filtrationwas filtered through Celite
  6. washthe filter pad was washed with water
  7. customThe filtrate layers were separated
  8. extractionthe aqueous layer was extracted again with ethyl acetate
  9. washwashed with brine
  10. dry with materialdried over sodium sulfate
  11. filtrationThe mixture was filtered
  12. concentrationconcentrated in vacuo
  13. customto give an oily solid which
  14. customwas purified by flash chromatography
  15. washeluting with heptanes/ethyl acetate (90:10 to 40:60)

Sources & evidence

ORD record
ord-a4549be7657241d9950389d5ae277df9
Source dataset
uspto-grants-2016_07
Patent number
US09394285B2

Reaction notes

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