Diisopropylamine → 1-(1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-2-(tetrahydro-pyran-2-yl)-ethanol

HRID 1515735Notes

Reaction equation

HRID 1515735 reaction equation
[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[CH:17][CH:18]=[C:13]3[CH:12]=[CH:11]2)(=[O:9])=[O:8])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C([N-]C(C)C)(C)C.[Li+].C([Li])CCC.CCCCCC.C(NC(C)C)(C)C.[O:45]1[CH2:50][CH2:49][CH2:48][CH2:47][CH:46]1[CH2:51][CH:52]=[O:53]>O1CCCC1>[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[CH:17][CH:18]=[C:13]3[CH:12]=[C:11]2[CH:52]([OH:53])[CH2:51][CH:46]2[CH2:47][CH2:48][CH2:49][CH2:50][O:45]2)(=[O:9])=[O:8])[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1

Participants

8

Reactant 6

HCID 7912DiisopropylamineHCID 8058HexaneHCID 8520781-(phenylsulfonyl)-1H-pyrrolo[2,3-b]pyridineHCID 2724682Lithium diisopropylamideHCID 537991492-(Oxan-2-yl)acetaldehydeHCID 178418339Butyllithium

Product 1

HCID 672296951-(1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-2-(tetrahydro-pyran-2-yl)-ethanolYield 60%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a suspension of 1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridine (5.0 g, 19.4 mmol) in dry tetrahydrofuran (125 mL) at −78° C. was added freshly prepared lithium diisopropylamide [prepared by adding 1.6 M n-butyllithium in n-hexane (18 mL, 29 mmol) to a 0° C. solution of diisopropylamine (4.4 mL, 31 mmol) in dry tetrahydrofuran (17 mL)] dropwise. The mixture was stirred at −78° C. for 5 min and then treated with (tetrahydro-pyran-2-yl)-acetaldehyde (4.6 g, 26 mmol) dropwise. The resulting mixture was stirred at −78° C. for 1 h and quenched with brine. The mixture was extracted with ethyl acetate (2×150 mL), washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. Purification by flash column chromatography (QingDao silica gel, 200-300 mesh, 25% ethyl acetate/hexanes) afforded 1-(1-benzenesulfonyl-1H-pyrrolo[2,3-b]pyridin-2-yl)-2-(tetrahydro-pyran-2-yl)-ethanol (4.5 g, 60%) as a colorless oil: LC/MS m/e calcd for C20H22N2O4S [M+H]+ 387.47, observed 387.2.

Workup

  1. customprepared
  2. stirringThe resulting mixture was stirred at −78° C. for 1 h
  3. customquenched with brine
  4. extractionThe mixture was extracted with ethyl acetate (2×150 mL)
  5. washwashed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customPurification by flash column chromatography (QingDao silica gel, 200-300 mesh, 25% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-ffb5e800cf924dc9a9860d66acb590dc
Source dataset
uspto-grants-2012_07
Patent number
US08222416B2

Reaction notes

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