5-Bromo-1-(triisopropylsilyl)-1H-indole → 3-[hydroxy-(1-triisopropylsilanyl-1H-indol-5-yl)-methyl]-3-phenyl-pyrrolidine-1-carboxylic acid methyl ester

HRID 661529Notes

Reaction equation

HRID 661529 reaction equation
C([Li])(C)(C)C.Br[C:7]1[CH:8]=[C:9]2[C:13](=[CH:14][CH:15]=1)[N:12]([Si:16]([CH:23]([CH3:25])[CH3:24])([CH:20]([CH3:22])[CH3:21])[CH:17]([CH3:19])[CH3:18])[CH:11]=[CH:10]2.[CH3:26][O:27][C:28]([N:30]1[CH2:34][CH2:33][C:32]([CH:41]=[O:42])([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH2:31]1)=[O:29]>C1COCC1>[CH3:26][O:27][C:28]([N:30]1[CH2:34][CH2:33][C:32]([CH:41]([OH:42])[C:7]2[CH:8]=[C:9]3[C:13](=[CH:14][CH:15]=2)[N:12]([Si:16]([CH:20]([CH3:21])[CH3:22])([CH:23]([CH3:25])[CH3:24])[CH:17]([CH3:19])[CH3:18])[CH:11]=[CH:10]3)([C:35]2[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=2)[CH2:31]1)=[O:29]

Participants

5

Reactant 3

HCID 27946525-Bromo-1-(triisopropylsilyl)-1H-indoleHCID 580172733-Formyl-3-phenyl-pyrrolidine-1-carboxylic acid methyl esterHCID 178418306HCID 178418306, compound

Product 1

HCID 580172393-[hydroxy-(1-triisopropylsilanyl-1H-indol-5-yl)-methyl]-3-phenyl-pyrrolidine-1-carboxylic acid methyl esterYield 51%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

tert-Butyllithium (1.7 M in pentane, 8.9 mL, 15.10 mmol) was added at −78° C., under nitrogen atmosphere to a solution of 5-bromo-1-triisopropylsilanyl-1H-indole (2.42 g, 6.86 mmol) in THF (25 mL). The resulting pale yellow solution was stirred at −78° C. for 15 minutes, then a solution of 3-formyl-3-phenyl-pyrrolidine-1-carboxylic acid methyl ester (1.60 g, 6.86 mmol) in THF (5 mL) was then slowly added. The reaction mixture was stirred at −78° C. for 30 minutes and then warmed to room temperature over a period of 1 hour. The reaction was quenched by addition of a saturated aqueous solution of NH4Cl and diluted with water. The resulting mixture was extracted with EtOAc, and the combined organic extracts were dried over MgSO4, filtered and evaporated under reduced pressure. The residue was purified by flash chromatography (10% to 50% of EtOAc in hexane) to give 1.76 g (51% yield) of 3-[hydroxy-(1-triisopropylsilanyl-1H-indol-5-yl)-methyl]-3-phenyl-pyrrolidine-1-carboxylic acid methyl ester as a white foamy solid.

Workup

  1. stirringThe reaction mixture was stirred at −78° C. for 30 minutes
  2. temperaturewarmed to room temperature over a period of 1 hour
  3. customThe reaction was quenched by addition of a saturated aqueous solution of NH4Cl
  4. additiondiluted with water
  5. extractionThe resulting mixture was extracted with EtOAc
  6. dry with materialthe combined organic extracts were dried over MgSO4
  7. filtrationfiltered
  8. customevaporated under reduced pressure
  9. customThe residue was purified by flash chromatography (10% to 50% of EtOAc in hexane)

Sources & evidence

ORD record
ord-68b97ab60d2540c1b9ef911713a6015f
Source dataset
uspto-grants-2011_12
Patent number
US08084623B2

Reaction notes

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