Allyl bromide → (r)-1-Allyl-5-bromo-3-(1-methyl-2-pyrrolidinylmethyl)-1h-indole

HRID 651708Notes

Reaction equation

HRID 651708 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].[CH3:18][C:19](C)([O-])[CH3:20].[K+].C(Br)C=C>>[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)[CH:19]=[CH2:18]

Participants

4

Reactant 3

HCID 7841Allyl bromideHCID 11185464(R)-5-Bromo-3-(1-methyl-2-pyrrolidinyl methyl)-1H-indoleHCID 23665647Potassium tert-butoxide

Product 1

HCID 54367533(r)-1-Allyl-5-bromo-3-(1-methyl-2-pyrrolidinylmethyl)-1h-indoleYield 78%

Procedure

To a stirred solution of (R)-5-bromo-3-(1-methyl-2-pyrrolidinylmethyl)-1H-indole (22.5 g, 76.8 mmol) in tetrahydroflran (132 ml) at 0° C. under a nitrogen atmosphere was added potassium tert-butoxide (9.47 g, 84.4 mmol) portionwise, maintaining the temperature below 5° C. Upon completion of the addition, the dark brown slurry was stirred at 0-5° C. for 30 min before allyl bromide (7.3 ml, 84.3 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 combined organic extracts were evaporated in vacuo to give a brown oil. This was purified by flash column chromatography (ethyl acetate:hexane:diethylamine 1:1:0.1 as eluant) to yield the subtitle compound (19.94 g, 78%) as a golden 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. customthe combined organic extracts were evaporated in vacuo
  8. customto give a brown oil
  9. customThis was purified by flash column chromatography (ethyl acetate:hexane:diethylamine 1:1:0.1 as eluant)

Sources & evidence

ORD record
ord-eca2731dbe0f4fae929b70920c2cdb56
Source dataset
uspto-grants-2001_08
Patent number
US06281357B1

Reaction notes

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