Benzyl Bromide → (r)-1-Benzyl-5-bromo-3-(1-methyl-2-pyrrolidinylmethyl)-1h-indole

HRID 651694Notes

Reaction equation

HRID 651694 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH:6]=[C:5]2[CH2:11][C@H:12]1[CH2:16][CH2:15][CH2:14][N:13]1[CH3:17].[H-].[Na+].[CH2:20](Br)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1>O1CCCC1>[CH2:20]([N:7]1[C:8]2[C:4](=[CH:3][C:2]([Br:1])=[CH:10][CH:9]=2)[C:5]([CH2:11][C@H:12]2[CH2:16][CH2:15][CH2:14][N:13]2[CH3:17])=[CH:6]1)[C:21]1[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 24758Sodium hydrideHCID 11185464(R)-5-Bromo-3-(1-methyl-2-pyrrolidinyl methyl)-1H-indole

Product 1

HCID 54492095(r)-1-Benzyl-5-bromo-3-(1-methyl-2-pyrrolidinylmethyl)-1h-indoleYield 63%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

To a stirred solution of (R)-5-bromo-3-(1-methyl-2-pyrrolidinylmethyl)-1H-indole (see Example 27, WO 92/06973) (21.44 g, 73.2 mmol) in tetrahydrofuran (110 ml) at 0° C. under a nitrogen atmosphere was added sodium hydride (60% dispersion in mineral oil, 3.51 g, 87.7 mmol) portionwise, maintaining the temperature below 5° C. Upon completion of the addition, the dark brown solution was stirred at 0-5° C. for 1 hr before benzyl bromide (10.4 ml, 87.4 mmol) was added dropwise maintaining the temperature below 5° C. The brown solution was then warmed to ambient temperature over a 1 hr period before being quenched into water (100 ml). The mixture was then extracted with ethyl acetate (3×25 ml) and the organic extracts were combined and evaporated in vacuo to yield a brown oil. This was purified by flash column chromatography (ethyl acetatehexane:diethylamine 1:1:0.1 as eluant) to give the subtitle compound (17.6 g, 63%) as a brown viscous oil.

Workup

  1. temperaturemaintaining the temperature below 5° C
  2. additionUpon completion of the addition
  3. additionwas added dropwise
  4. temperaturemaintaining the temperature below 5° C
  5. custombefore being quenched into water (100 ml)
  6. extractionThe mixture was then extracted with ethyl acetate (3×25 ml)
  7. customevaporated in vacuo
  8. customto yield a brown oil
  9. customThis was purified by flash column chromatography (ethyl acetatehexane:diethylamine 1:1:0.1 as eluant)

Sources & evidence

ORD record
ord-8f96ef47ac0f4330b282137778ce946f
Source dataset
uspto-grants-2001_08
Patent number
US06281357B1

Reaction notes

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