Diisopropylamine → 1-(1-benzenesulfonyl-5-methoxy-1H-pyrrolo[2,3-b]pyridin-2-yl)-2-(tetrahydro-pyran-4-yl)-ethanol

HRID 1515660Notes

Reaction equation

HRID 1515660 reaction equation
[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([O:19][CH3:20])[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:47]1[CH2:52][CH2:51][CH:50]([CH2:53][CH:54]=[O:55])[CH2:49][CH2:48]1>O1CCCC1>[C:1]1([S:7]([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([O:19][CH3:20])[CH:18]=[C:13]3[CH:12]=[C:11]2[CH:54]([OH:55])[CH2:53][CH:50]2[CH2:51][CH2:52][O:47][CH2:48][CH2:49]2)(=[O:8])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

8

Reactant 6

HCID 7912DiisopropylamineHCID 8058HexaneHCID 2724682Lithium diisopropylamideHCID 177509432-(Oxan-4-yl)acetaldehydeHCID 222736501H-Pyrrolo[2,3-B]pyridine, 5-methoxy-1-(phenylsulfonyl)-HCID 178418339Butyllithium

Product 1

HCID 672281561-(1-benzenesulfonyl-5-methoxy-1H-pyrrolo[2,3-b]pyridin-2-yl)-2-(tetrahydro-pyran-4-yl)-ethanolYield 77.2%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
-78 °C

Procedure

To a suspension of 1-benzenesulfonyl-5-methoxy-1H-pyrrolo[2,3-b]pyridine (prepared as in Example 10, 4 g, 13.9 mmol) in dry tetrahydrofuran (60 mL) at −78° C. was added freshly prepared lithium diisopropylamide [prepared by adding 1.6 M n-butyllithium in n-hexane (13 mL, 20.83 mmol) to a 0° C. solution of diisopropylamine (3.2 mL, 22.1 mmol) in dry tetrahydrofuran (20 mL)] dropwise. The mixture was stirred at −78° C. for 5 min and then treated with (tetrahydro-pyran-4-yl)-acetaldehyde (2.67 g, 20.8 mmol) dropwise. The resulting mixture was stirred at −78° C. for 1 h and quenched with brine. The mixture was extracted with ethyl acetate (2×300 mL), washed with brine, dried over anhydrous sodium sulfate and concentrated in vacuo. Purification by flash silica gel chromatography (silica gel from QingDao, 200-300 mesh, glass column from Shanghai SD company, 33% ethyl acetate/hexanes) afforded 1-(1-benzenesulfonyl-5-methoxy-1H-pyrrolo[2,3-b]pyridin-2-yl)-2-(tetrahydro-pyran-4-yl)-ethanol as a white solid (4.4 g, 77.2%): LC/MS m/e calcd for C21H24N2O5S [M+H]+ 417.50, observed 417.1.

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 (2×300 mL)
  5. washwashed with brine
  6. dry with materialdried over anhydrous sodium sulfate
  7. concentrationconcentrated in vacuo
  8. customPurification by flash silica gel chromatography (silica gel from QingDao, 200-300 mesh, glass column from Shanghai SD company, 33% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-9f42923ca17a4e5f9263e86ce679beec
Source dataset
uspto-grants-2012_07
Patent number
US08222416B2

Reaction notes

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