Potassium Phosphate, Tribasic → 4-[(phenylmethyl)oxy]-1-{4-[(phenylmethyl)oxy]phenyl}-1H-indole

HRID 2421249Notes

Reaction equation

HRID 2421249 reaction equation
[C:1]1([CH2:7][O:8][C:9]2[CH:17]=[CH:16][CH:15]=[C:14]3[C:10]=2[CH:11]=[CH:12][NH:13]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:18]1([CH2:24][O:25][C:26]2[CH:31]=[CH:30][C:29](Br)=[CH:28][CH:27]=2)[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1.[O-]P([O-])([O-])=O.[K+].[K+].[K+].N1CCC[C@H]1C(O)=O>O1CCOCC1>[C:1]1([CH2:7][O:8][C:9]2[CH:17]=[CH:16][CH:15]=[C:14]3[C:10]=2[CH:11]=[CH:12][N:13]3[C:29]2[CH:30]=[CH:31][C:26]([O:25][CH2:24][C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)=[CH:27][CH:28]=2)[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

6

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 884654-(phenylmethoxy)-1H-indoleHCID 1388351-Bromo-4-phenylmethoxybenzeneHCID 145742L-Proline

Product 1

HCID 596279224-[(phenylmethyl)oxy]-1-{4-[(phenylmethyl)oxy]phenyl}-1H-indoleYield 16%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

4-[(phenylmethyl)oxy]-1H-indole (504 mg, 2.26 mmoL), 4-bromophenyl phenylmethyl ether (580 mg, 1.88 mmoL), K3PO4 (998 mg, 4.7 mmoL) and L-Proline (43.3 mg, 0.376 mmoL) were dissolved in 1,4-Dioxane (4 mL) in a microwave vial and degassed by sonication under a flow of argon. To this was added CuI (18 mg, 0.094 mmoL) and the solution was heated to 100° C. in the microwave reactor. After 5 hours a second portion of CuI (48 mg, 0.252 mmoL) and L-Proline (40 mg, 0.347 mmoL) were added and the mixture heated for 2 more hours. The reaction mixture was filtered through a pad of celite and concentrated. The residue was partitioned between ethyl acetate (100 mL)/water (100 mL), the phases were separated and the aqueous phase re-extracted with ethyl acetate (100 mL). The combined organic phases were washed with brine (2×50 mL) then water (50 mL) and finally dried over MgSO4. The crude product was purified by flash chromatography (Biotage SP4) eluting with a gradient of 0 to 30% Et2O in hexane to give the title compound (D24), (143 mg).

Workup

  1. customdegassed by sonication under a flow of argon
  2. additionTo this was added CuI (18 mg, 0.094 mmoL)
  3. additionAfter 5 hours a second portion of CuI (48 mg, 0.252 mmoL) and L-Proline (40 mg, 0.347 mmoL) were added
  4. temperaturethe mixture heated for 2 more hours
  5. filtrationThe reaction mixture was filtered through a pad of celite
  6. concentrationconcentrated
  7. customThe residue was partitioned between ethyl acetate (100 mL)/water (100 mL)
  8. customthe phases were separated
  9. extractionthe aqueous phase re-extracted with ethyl acetate (100 mL)
  10. washThe combined organic phases were washed with brine (2×50 mL)
  11. dry with materialwater (50 mL) and finally dried over MgSO4
  12. customThe crude product was purified by flash chromatography (Biotage SP4)
  13. washeluting with a gradient of 0 to 30% Et2O in hexane

Sources & evidence

ORD record
ord-ecda2e270b8a40ba984591c73cf04cc8
Source dataset
uspto-grants-2011_06
Patent number
US07956083B2

Reaction notes

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