5-Bromo-1-(triisopropylsilyl)-1H-indole → 2-benzyl-2-(1-triisopropylsilanyl-1H-indole-5-carbonyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1895012Notes

Reaction equation

HRID 1895012 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[CH:6]=[CH:5]2.C([Li])(C)(C)C.C[O:27][C:28]([C@:30]1([CH2:42][C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[CH2:34][CH2:33][CH2:32][N:31]1[C:35]([O:37][C:38]([CH3:41])([CH3:40])[CH3:39])=[O:36])=O>C1COCC1>[C:38]([O:37][C:35]([N:31]1[CH2:32][CH2:33][CH2:34][C:30]1([CH2:42][C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1)[C:28]([C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[N:7]([Si:11]([CH:15]([CH3:16])[CH3:17])([CH:18]([CH3:19])[CH3:20])[CH:12]([CH3:13])[CH3:14])[CH:6]=[CH:5]2)=[O:27])=[O:36])([CH3:41])([CH3:39])[CH3:40]

Participants

5

Reactant 3

HCID 27946525-Bromo-1-(triisopropylsilyl)-1H-indoleHCID 66687350HCID 66687350, compoundHCID 178418306HCID 178418306, compound

Product 1

HCID 666880832-benzyl-2-(1-triisopropylsilanyl-1H-indole-5-carbonyl)-pyrrolidine-1-carboxylic acid tert-butyl esterYield 16.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a stirred solution of 5-bromo-1-triisopropylsilanyl-1H-indole (0.55 g, 1.57 mmol) in THF (10 mL) at −78° C. under nitrogen atmosphere was added tert-butyllithium (2.02 mL of 1.55 M solution in pentanes, 3.13 mmol) dropwise. After one hour, the reaction mixture was added rapidly to a cold (−78° C.) solution of (R)-2-benzyl-pyrrolidine-1,2-dicarboxylic acid 1-tert-butyl ester 2-methyl ester (0.50 g, 3.13 mmol) in THF (10 mL). The reaction mixture was stirred at −78° C. for one hour, then warmed to room temperature and stirred for two hours. The reaction mixture was quenched by the addition of saturated aqueous NH4Cl (20 mL) then extracted with EtOAc. The combined extracts were washed with brine then dried (MgSO4), filtered and concentrated in vacuo. Purification by chromatography (silica, 0-20% EtOAc in hexanes) gave 2-benzyl-2-(1-triisopropylsilanyl-1H-indole-5-carbonyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (0.145 g, 0.259 mmol, 16%) as a colourless gum.

Workup

  1. temperaturewarmed to room temperature
  2. stirringstirred for two hours
  3. customThe reaction mixture was quenched by the addition of saturated aqueous NH4Cl (20 mL)
  4. extractionthen extracted with EtOAc
  5. washThe combined extracts were washed with brine
  6. dry with materialthen dried (MgSO4)
  7. filtrationfiltered
  8. concentrationconcentrated in vacuo
  9. customPurification by chromatography (silica, 0-20% EtOAc in hexanes)

Sources & evidence

ORD record
ord-a1ab3794b930430aba0dce29535c8da4
Source dataset
uspto-grants-2013_08
Patent number
US08513425B2

Reaction notes

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