Triethylamine → 3-{2-[2-(4-bromophenyl)pyrrolidin-1-yl]ethyl}-2-methyl-1H-indole

HRID 549377Notes

Reaction equation

HRID 549377 reaction equation
[Br:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:12][CH2:11][CH2:10][NH:9]2)=[CH:4][CH:3]=1.[CH3:13][C:14]1[NH:15][C:16]2[C:21]([C:22]=1[CH2:23][CH:24]=O)=[CH:20][CH:19]=[CH:18][CH:17]=2.C(N(CC)CC)C.C([BH3-])#N.[Na+].[OH-].[Na+]>ClCCl.[Ti](Cl)(Cl)(Cl)Cl>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([CH:8]2[CH2:12][CH2:11][CH2:10][N:9]2[CH2:24][CH2:23][C:22]2[C:21]3[C:16](=[CH:17][CH:18]=[CH:19][CH:20]=3)[NH:15][C:14]=2[CH3:13])=[CH:6][CH:7]=1

Participants

8

Reactant 5

HCID 8471TriethylamineHCID 14798Sodium HydroxideHCID 42814942-(4-Bromophenyl)pyrrolidineHCID 5003444Sodium cyanoborohydrideHCID 591586672-(2-methyl-1H-indol-3-yl)acetaldehyde

Product 1

HCID 461979023-{2-[2-(4-bromophenyl)pyrrolidin-1-yl]ethyl}-2-methyl-1H-indoleYield 114.1%

Reagents, catalysts & solvents 2

HCID 24193Titanium TetrachlorideCatalystHCID 6344DichloromethaneSolvent2×

Procedure

To a solution of 2-(4-bromo-phenyl)-pyrrolidine (326 mg, 1.44 mmol) in dichloromethane (20 mL) were added (2-methyl-1H-indol-3-yl)-acetaldehyde (250 mg, 1.44 mmol), triethylamine (0.603 mL, 4.33 mmol) and a solution of titanium (IV) chloride in dichloromethane (0.720 mL, 1 M, 0.72 mmol), and the resulting mixture was stirred at room temperature. The reaction mixture was treated with sodium cyanoborohydride (286 mg, 4.32 mmol), stirred for 2 h, basified to pH 13 with an aqueous 5 N sodium hydroxide solution, and extracted with ethyl acetate. The organic layers were combined, dried over magnesium sulfate, filtered and concentrated to provide a crude product, which was purified on silica gel column chromatography to give 3-{2-[2-(4-bromo-phenyl)-pyrrolidin-1-yl]-ethyl}-2-methyl-1H-indole (630 mg, 99% yield). LCMS (m/z): 384.84 (M+1).

Workup

  1. extractionextracted with ethyl acetate
  2. dry with materialdried over magnesium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customto provide a crude product, which
  6. customwas purified on silica gel column chromatography

Sources & evidence

ORD record
ord-c21f6d2d480e4c03bc01d7fce4c7095b
Source dataset
uspto-grants-2011_05
Patent number
US07943652B2

Reaction notes

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