Potassium Phosphate, Tribasic → 2-(3-benzyloxy-phenyl)-6-chloro-1H-indole

HRID 1630850Notes

Reaction equation

HRID 1630850 reaction equation
[Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[C:7](B(O)O)[N:8]2C(OC(C)(C)C)=O)=[CH:4][CH:3]=1.[CH2:21]([O:28]N1C=CC=C(Br)C1)[C:22]1[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.CN(C=O)C>[CH2:21]([O:28][C:2]1[CH:3]=[C:4]([C:7]2[NH:8][C:9]3[C:5]([CH:6]=2)=[CH:4][CH:3]=[C:2]([Cl:1])[CH:10]=3)[CH:5]=[CH:9][CH:10]=1)[C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=1

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 441191511-Boc-6-chloroindole-2-boronic acidHCID 670938311-Benzyloxy-3-bromo-pyridine

Product 1

HCID 670934712-(3-benzyloxy-phenyl)-6-chloro-1H-indole

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A flask is charged with 6-chloro-1-Boc-indole-2-boronic acid (0.839 g, 2.83 mmol), 1-benzyloxy-3-bromo-pyridine (0.500 g, 1.89 mmol), potassium phosphate (1.2 g, 5.67 mmol) and DMF (5 mL). The flask is evacuated and filled with nitrogen thrice and Pd(PPh3)4 (0.164 g, 0.141 mmol) is added. The flask is evacuated and filled with nitrogen thrice again, and heated to 80° C. for 3.5 h. The mixture is then diluted with ethyl acetate and washed with water thrice. The organic layer is dried over sodium sulfate and concentrated in vacuo. The residue is redissolved in DCM (1 mL) and trifluoroacetic acid (2 mL) is added. After 1 h, 4M aqueous NaOH is added and following extraction with DCM, the organic layer is dried over sodium sulfate and concentrated in vacuo. The residue is purified by silica gel flash chromatography (heptane-ethyl acetate, 1:1) to afford 2-(3-benzyloxy-phenyl)-6-chloro-1H-indole as a yellow solid. MS (ESI) m/z 335.07 (M+H)+.

Workup

  1. customThe flask is evacuated
  2. additionis added
  3. customThe flask is evacuated
  4. additionfilled with nitrogen thrice again
  5. additionThe mixture is then diluted with ethyl acetate
  6. washwashed with water thrice
  7. dry with materialThe organic layer is dried over sodium sulfate
  8. concentrationconcentrated in vacuo
  9. dissolutionThe residue is redissolved in DCM (1 mL)
  10. additiontrifluoroacetic acid (2 mL) is added
  11. addition4M aqueous NaOH is added
  12. extractionextraction with DCM
  13. dry with materialthe organic layer is dried over sodium sulfate
  14. concentrationconcentrated in vacuo
  15. customThe residue is purified by silica gel flash chromatography (heptane-ethyl acetate, 1:1)

Sources & evidence

ORD record
ord-928e8f597ea74acf9e91125bc58b31d9
Source dataset
uspto-grants-2014_07
Patent number
US08791141B2

Reaction notes

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