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

HRID 1894995Notes

Reaction equation

HRID 1894995 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-38be54d0baa44671bd052f964f127a1a
Source dataset
uspto-grants-2013_08
Patent number
US08513425B2

Reaction notes

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