Isopropylamine → 1,1-dimethylethyl 4-[4-bromo-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-4-hydroxy-1-piperidinecarboxylate

HRID 28999Notes

Reaction equation

HRID 28999 reaction equation
[CH:1](N)([CH3:3])[CH3:2].[Li][CH2:6]CCC.[Br:10][C:11]1[CH:16]=[CH:15][N:14]=[C:13]2[N:17]([S:20]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)(=[O:22])=[O:21])[CH:18]=[CH:19][C:12]=12.CC([CH:33]1[CH2:38][C:37](=[O:39])[CH2:36][CH2:35][N:34]1[C:40]([O-:42])=[O:41])(C)C>C1COCC1>[Br:10][C:11]1[CH:16]=[CH:15][N:14]=[C:13]2[N:17]([S:20]([C:23]3[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=3)(=[O:22])=[O:21])[C:18]([C:37]3([OH:39])[CH2:38][CH2:33][N:34]([C:40]([O:42][C:1]([CH3:3])([CH3:6])[CH3:2])=[O:41])[CH2:35][CH2:36]3)=[CH:19][C:12]=12

Participants

6

Reactant 4

HCID 6363IsopropylamineHCID 450745614-Bromo-1-(phenylsulfonyl)-1H-pyrrolo[2,3-B]pyridineHCID 866133321,1-Dimethylethyl-4-oxo-1-piperidinecarboxylateHCID 178418339Butyllithium

Product 1

HCID 689960751,1-dimethylethyl 4-[4-bromo-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridin-2-yl]-4-hydroxy-1-piperidinecarboxylateYield 85%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent3×

Conditions

Temperature
-78 °C

Procedure

To a solution of isopropylamine (5.5 mmol) in THF (15 mL) cooled to −78° C. was added n-BuLi (2.5 M in hexanes, 5.5 mmol) dropwise. After stirring at −78° C. for 20 min a solution of 4-bromo-1-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridine (5.0 mmol) in THF (5.0 mL) was added dropwise. The resulting orange solution was stirred at −78° C. for 2 h, followed by dropwise addition of a solution of 1,1-dimethylethyl-4-oxo-1-piperidinecarboxylate (6.1 mmol) in THF (5.0 mL). After an additional 1.5 h at −78° C., the reaction mixture was warmed to room temperature and quenched with saturated NH4Cl(aq). Extraction with EtOAc (3□), washing with brine, drying (Na2SO4), filtration and concentrated in vacuo provided crude material which was purified by flash chromatography (120 g SiO2, 0-5% EtOAc in CHCl3) to give the title compound as a white solid (85%). ESMS [M+H]+: 536.0.

Workup

  1. additionwas added dropwise
  2. waitAfter an additional 1.5 h at −78° C.
  3. temperaturethe reaction mixture was warmed to room temperature
  4. customquenched with saturated NH4Cl(aq)
  5. extractionExtraction with EtOAc (3□)
  6. washwashing with brine
  7. customdrying
  8. filtration(Na2SO4), filtration
  9. concentrationconcentrated in vacuo
  10. customprovided crude material which
  11. customwas purified by flash chromatography (120 g SiO2, 0-5% EtOAc in CHCl3)

Sources & evidence

ORD record
ord-c9353e7c5e9e4afc9d5cff6f0fad58f1
Source dataset
uspto-grants-2008_09
Patent number
US07419988B2

Reaction notes

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