5-Bromo-1-(triisopropylsilyl)-1H-indole → 3-(1-triisopropylsilanyl-1H-indole-5-carbonyl)-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1894994Notes

Reaction equation

HRID 1894994 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.[C:26]([O:30][C:31]([N:33]1[CH2:37][CH2:36][CH:35]([C:38](=[O:43])N(OC)C)[CH2:34]1)=[O:32])([CH3:29])([CH3:28])[CH3:27]>C1COCC1>[C:26]([O:30][C:31]([N:33]1[CH2:37][CH2:36][CH:35]([C:38]([C:7]2[CH:8]=[C:9]3[C:13](=[CH:14][CH:15]=2)[N:12]([Si:16]([CH:17]([CH3:18])[CH3:19])([CH:20]([CH3:22])[CH3:21])[CH:23]([CH3:24])[CH3:25])[CH:11]=[CH:10]3)=[O:43])[CH2:34]1)=[O:32])([CH3:29])([CH3:28])[CH3:27]

Participants

5

Reactant 3

HCID 27946525-Bromo-1-(triisopropylsilyl)-1H-indoleHCID 57419605Tert-butyl 3-[methoxy(methyl)carbamoyl]pyrrolidine-1-carboxylateHCID 178418306HCID 178418306, compound

Product 1

HCID 666875723-(1-triisopropylsilanyl-1H-indole-5-carbonyl)-pyrrolidine-1-carboxylic acid tert-butyl esterYield 56.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

tert-Butyllithium (1.7 M in pentane, 13 mL, 22.13 mmol) was added to a solution of 5-bromo-1-triisopropylsilanyl-1H-indole (3.54 g, 10.06 mmol) in THF (35 mL) at −78° C. under nitrogen atmosphere. The pale yellow reaction mixture was stirred at −78° C. for 15 minutes, then a solution of 3-(methoxy-methyl-carbamoyl)-pyrrolidine-1-carboxylic acid tert-butyl ester (2.60 g, 10.06 mmol) in THF (5 mL) was slowly added. The resulting mixture was stirred at −78° C. for 30 minutes, then allowed to warm to room temperature over a period of 1 hour. The reaction was quenched by addition of a saturated aqueous solution of NH4Cl and was partitioned between water and EtOAc. The organic layer was dried over MgSO4, filtered and evaporated under reduced pressure. The crude residue was purified by flash chromatography (10% to 25% of EtOAc in hexane) to give 2.66 g (56% yield) of 3-(1-triisopropylsilanyl-1H-indole-5-carbonyl)-pyrrolidine-1-carboxylic acid tert-butyl ester as colorless oil.

Workup

  1. stirringThe resulting mixture was stirred at −78° C. for 30 minutes
  2. temperatureto warm to room temperature over a period of 1 hour
  3. customThe reaction was quenched by addition of a saturated aqueous solution of NH4Cl
  4. customwas partitioned between water and EtOAc
  5. dry with materialThe organic layer was dried over MgSO4
  6. filtrationfiltered
  7. customevaporated under reduced pressure
  8. customThe crude residue was purified by flash chromatography (10% to 25% of EtOAc in hexane)

Sources & evidence

ORD record
ord-653bf15558274766ba24b2807f54b4ef
Source dataset
uspto-grants-2013_08
Patent number
US08513425B2

Reaction notes

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