Benzyl Bromide → 3-benzyl-3-(1-triisopropylsilanyl-1H-indole-5-carbonyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 661519Notes

Reaction equation

HRID 661519 reaction equation
C[Si]([N-][Si](C)(C)C)(C)C.[Li+].[C:11]([O:15][C:16]([N:18]1[CH2:22][CH2:21][CH:20]([C:23]([C:25]2[CH:26]=[C:27]3[C:31](=[CH:32][CH:33]=2)[N:30]([Si:34]([CH:41]([CH3:43])[CH3:42])([CH:38]([CH3:40])[CH3:39])[CH:35]([CH3:37])[CH3:36])[CH:29]=[CH:28]3)=[O:24])[CH2:19]1)=[O:17])([CH3:14])([CH3:13])[CH3:12].[CH2:44](Br)[C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1>C1COCC1>[C:11]([O:15][C:16]([N:18]1[CH2:22][CH2:21][C:20]([CH2:44][C:45]2[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=2)([C:23]([C:25]2[CH:26]=[C:27]3[C:31](=[CH:32][CH:33]=2)[N:30]([Si:34]([CH:35]([CH3:36])[CH3:37])([CH:38]([CH3:40])[CH3:39])[CH:41]([CH3:43])[CH3:42])[CH:29]=[CH:28]3)=[O:24])[CH2:19]1)=[O:17])([CH3:13])([CH3:14])[CH3:12]

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 2733832Lithium HexamethyldisilazideHCID 666875723-(1-triisopropylsilanyl-1H-indole-5-carbonyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

Product 1

HCID 666879163-benzyl-3-(1-triisopropylsilanyl-1H-indole-5-carbonyl)-pyrrolidine-1-carboxylic acid tert-butyl esterYield 69%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
0 °C

Procedure

Lithium bis(trimethylsilyl)amide (1.0 M in THF, 12.1 mL) was added to a solution of 3-(1-triisopropylsilanyl-1H-indole-5-carbonyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (1.90 g, 4.03 mmol) in THF (25 mL) at 0° C. under nitrogen atmosphere. The reaction mixture was stirred at 0° C. for 10 minutes and then benzyl bromide (1.9 mL, 16.12 mmol) was added. The resulting mixture was warmed to room temperature and stirred for 1.5 hours. The reaction was quenched by addition of a saturated aqueous solution of NH4Cl, then diluted with water and extracted with EtOAc. The organic layer was dried over MgSO4, filtered and evaporated under reduced pressure. The residue was purified by flash chromatography (10% to 20% of EtOAc in hexane) to give 1.55 g (69% yield) of 3-benzyl-3-(1-triisopropylsilanyl-1H-indole-5-carbonyl)-pyrrolidine-1-carboxylic acid tert-butyl ester as a white foam.

Workup

  1. temperatureThe resulting mixture was warmed to room temperature
  2. stirringstirred for 1.5 hours
  3. customThe reaction was quenched by addition of a saturated aqueous solution of NH4Cl
  4. additiondiluted with water
  5. extractionextracted with EtOAc
  6. dry with materialThe organic layer was dried over MgSO4
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customThe residue was purified by flash chromatography (10% to 20% of EtOAc in hexane)

Sources & evidence

ORD record
ord-6fd9eb09921545bf8aebc0026fdce82e
Source dataset
uspto-grants-2011_12
Patent number
US08084623B2

Reaction notes

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