Indole → HCID 14221129, compound

HRID 1486769Notes

Reaction equation

HRID 1486769 reaction equation
[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:3]=[CH:2]1.[Li]CCCC.[CH2:15](Br)[CH:16]=[C:17]([CH3:19])[CH3:18]>C1COCC1>[CH2:15]([C:2]1[NH:1][C:9]2[C:4]([CH:3]=1)=[CH:5][CH:6]=[CH:7][CH:8]=2)[CH:16]=[C:17]([CH3:19])[CH3:18]

Participants

5

Reactant 3

HCID 798IndoleHCID 700922-Butene, 1-bromo-3-methyl-HCID 178418339Butyllithium

Product 1

HCID 14221129HCID 14221129, compound

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To silyl protected indole B (724 mmol, 1.52 mmol) in THF was added a few 4 Å molecular sieves and the mixture was cooled to −78° C. After n-BuLi (0.75 ml, 2.3M in hexanes) was added, the mixture was stirred for 20 min and prenyl bromide (420 mmol, 2.82 mmol) was added. The next day the reaction mixture was quenched by addition of NH4Cl (sat), and extracted with Et2O. The combined organic layers were washed with brine, dried (MgSO4), and filtered, and the filtrated was concentrated in vacuo. Final purification by flash column chromatography (5% EtOAc in hexanes) afforded prenyl indole C (560 mg, 68%) as well as recovered starting material (76 mg, 10%): 1H NMR δ 7.91 (d, J=0.8 Hz, 1H), 7.73 (d, J=8.4 Hz, 2H), 7.25, (d, J=8.5 Hz, 2H), 6.99 (s, 1H), 6.52 (d, J=0.8 Hz, 1H), 5.47 (m, 1H), 5.31 (s, 2H), 4.90 (s, 2H), 3.74 (d, J=7.2 Hz, 2H), 3.55 (s, 3H), 2.40 (s, 3H), 1.86 (s, 3H), 1.71 (s, 3H) 1.05 (s, 9H), 0.20 (s, 6H); 13C NMR δ 149.5, 144.5, 139.9, 138.7, 138.6, 136.5, 134.5, 129.7 (2C), 126.3 (2C), 119.8, 119.6, 106.5, 106.3, 105.3, 94.8, 65.5, 56.0, 27.9, 25.9 (3C), 25.7, 21.4, 18.3, 17.7, −5.2 (2C); HRMS (EI+) calcd for C29H41NO5SSi [M+] 543.2475. found 543.2476.

Workup

  1. additionwas added a few 4 Å molecular sieves
  2. customThe next day the reaction mixture was quenched by addition of NH4Cl (sat)
  3. extractionextracted with Et2O
  4. washThe combined organic layers were washed with brine
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. concentrationthe filtrated was concentrated in vacuo
  8. customFinal purification by flash column chromatography (5% EtOAc in hexanes)

Sources & evidence

ORD record
ord-070b5f9e2e734ba093d6c31c795c0e8e
Source dataset
uspto-grants-2016_08
Patent number
US09428493B2

Reaction notes

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