5-Bromo-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridine → 2-[hydroxy-(1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-methyl]-2-propyl-pyrrolidine-1-carboxylic acid tert-butyl ester

HRID 1895021Notes

Reaction equation

HRID 1895021 reaction equation
Br[C:2]1[CH:3]=[C:4]2[CH:10]=[CH:9][N:8]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[C:5]2=[N:6][CH:7]=1.C([Li])(C)(C)C.[C:26]([O:30][C:31]([N:33]1[CH2:37][CH2:36][CH2:35][C:34]1([CH:41]=[O:42])[CH2:38][CH2:39][CH3:40])=[O:32])([CH3:29])([CH3:28])[CH3:27]>CCOCC>[C:26]([O:30][C:31]([N:33]1[CH2:37][CH2:36][CH2:35][C:34]1([CH:41]([OH:42])[C:2]1[CH:3]=[C:4]2[CH:10]=[CH:9][N:8]([Si:11]([CH:18]([CH3:20])[CH3:19])([CH:15]([CH3:17])[CH3:16])[CH:12]([CH3:14])[CH3:13])[C:5]2=[N:6][CH:7]=1)[CH2:38][CH2:39][CH3:40])=[O:32])([CH3:28])([CH3:29])[CH3:27]

Participants

5

Reactant 3

HCID 242292235-Bromo-1-(triisopropylsilyl)-1H-pyrrolo[2,3-b]pyridineHCID 866208602-Formyl-2-propyl-pyrrolidine-1-carboxylic acid tert-butyl esterHCID 178418306HCID 178418306, compound

Product 1

HCID 666875152-[hydroxy-(1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-methyl]-2-propyl-pyrrolidine-1-carboxylic acid tert-butyl esterYield 67.5%

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent2×

Procedure

To a stirred solution of 5-bromo-1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridine (0.587 g, 1.66 mmol) in ether (20 mL) at −78° C. and under nitrogen was added tert-butyllithium (2.30 mL of 1.51 M solution in pentanes, 3.49 mmol) dropwise. After 90 minutes, a solution of 2-formyl-2-propyl-pyrrolidine-1-carboxylic acid tert-butyl ester (0.400 g, 1.66 mmol) in ether (1 mL) was added to the reaction mixture dropwise. After stirring for one hour, the reaction mixture was warmed to ambient temperature over 30 minutes. The reaction mixture was quenched by the addition of saturated aqueous NH4Cl (20 mL) then extracted with EtOAc. The combined extracts were washed with saturated aqueous NaHCO3 and brine, then dried (MgSO4), filtered and concentrated in vacuo to a yellow oil (0.90 g). Purification by chromatography (silica, 5-20% EtOAc in hexanes) gave 2-[hydroxy-(1-triisopropylsilanyl-1H-pyrrolo[2,3-b]pyridin-5-yl)-methyl]-2-propyl-pyrrolidine-1-carboxylic acid tert-butyl ester (0.576 g, 1.12 mmol, 53%) as a colourless gum.

Workup

  1. customThe reaction mixture was quenched by the addition of saturated aqueous NH4Cl (20 mL)
  2. extractionthen extracted with EtOAc
  3. washThe combined extracts were washed with saturated aqueous NaHCO3 and brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo to a yellow oil (0.90 g)
  7. customPurification by chromatography (silica, 5-20% EtOAc in hexanes)

Sources & evidence

ORD record
ord-35e8583f3c284432a1344ffddd6428bd
Source dataset
uspto-grants-2013_08
Patent number
US08513425B2

Reaction notes

Loading…