Boron tribromide → 6-(1-Benzyl-3-pentyl-1H-indol-2-yl)-2-naphthol

HRID 898289Notes

Reaction equation

HRID 898289 reaction equation
[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])=[C:9]1[C:22]1[CH:31]=[CH:30][C:29]2[C:24](=[CH:25][CH:26]=[C:27]([O:32]C)[CH:28]=2)[CH:23]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.B(Br)(Br)Br>C(Cl)Cl.C(Cl)(Cl)Cl>[CH2:1]([N:8]1[C:16]2[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=2)[C:10]([CH2:17][CH2:18][CH2:19][CH2:20][CH3:21])=[C:9]1[C:22]1[CH:23]=[C:24]2[C:29](=[CH:30][CH:31]=1)[CH:28]=[C:27]([OH:32])[CH:26]=[CH:25]2)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 2

HCID 25134Boron tribromideHCID 223273361-benzyl-2-(6-methoxy-2-naphthyl)-3-pentyl-1H-indole

Product 1

HCID 223273436-(1-Benzyl-3-pentyl-1H-indol-2-yl)-2-naphtholYield 85%

Reagents, catalysts & solvents 2

HCID 6212ChloroformSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of the 1-benzyl-2-(6-methoxy-2-naphthyl)-3-pentyl-1H-indole (109.0 g, 251 mmol) in CH2Cl2 (1000 mL) under N2 at −78° C. was added BBr3 (1M in CH2Cl2, 302 mL), dropwise, over 1.5 h. After the addition, the reaction was warmed to 0° C. and stirred for 2.5 h then warmed to rt. After a total of 5 h the reaction mixture was cooled to 0° C. and quenched with water (250 mL). The mixture was stirred overnight then rotovap'd to a residue. The residue was partitioned between EtOAc (1500 mL) and H2O (500 mL). The layers were shaken, separated, and the organic layer was washed with H2O (2×250 mL), brine (2×250 mL), dried over Na2SO4, filtered, rotovap'd and dried in vacuo to give a viscous black goo (114 g). The residue was dissolved in CHCl3 and flashed on silica (2000 g). The column was eluted with hexane and 8% EtOAc/Hexane. The product was collected, filtered, rotovap'd and the residue triturated with hexane then dried to give the product as an off-white solid (89.2 g, 213 mmol, 85%) with mp 96-100° C. 400mg of the crude solid was recrystallized from hexane to give desired product as an off-white solid (311 mg) with mp 97-100° C.; 1H NMR (DMSO-d6) δ 0.73 (t, J=6.7 Hz, 3H), 1.10-1.20 (m, 4H), 1.51-1.60 (m, 2H), 2.67 (t, J=7.3 Hz, 3H), 5.29 (s, 2H), 6.82 (d, J=7.2 Hz, 2H), 7.04-7.20 (m, 7H), 7.30-7.35 (m, 2H), 7.59 (d, J=7.8 Hz, 1H), 7.73-7.78 (m, 3H); IR (solid) 3380, 2920, 1610, 1200, 740 cm−1; mass spectrum [ES], m/z 420 (M+H)+;

Workup

  1. additionAfter the addition
  2. temperaturethen warmed to rt
  3. temperatureAfter a total of 5 h the reaction mixture was cooled to 0° C.
  4. customquenched with water (250 mL)
  5. stirringThe mixture was stirred overnight
  6. customThe residue was partitioned between EtOAc (1500 mL) and H2O (500 mL)
  7. stirringThe layers were shaken
  8. customseparated
  9. washthe organic layer was washed with H2O (2×250 mL), brine (2×250 mL)
  10. dry with materialdried over Na2SO4
  11. filtrationfiltered
  12. customdried in vacuo
  13. customto give a viscous black goo (114 g)
  14. washThe column was eluted with hexane and 8% EtOAc/Hexane
  15. customThe product was collected
  16. filtrationfiltered
  17. customrotovap'd and the residue triturated with hexane
  18. customthen dried

Sources & evidence

ORD record
ord-18c787e05fcb4c47a334f589971b030a
Source dataset
uspto-grants-2008_04
Patent number
US07351730B2

Reaction notes

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