Hexane → (1-benzenesulfonyl-5-methoxy-1H-pyrrolo[2,3-b]pyridin-2-yl)-(4-methylsulfanyl-3-trifluoromethyl-phenyl)-methanol

HRID 1515770Notes

Reaction equation

HRID 1515770 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([Li])CCC.CCCCCC.[CH3:32][S:33][C:34]1[CH:41]=[CH:40][C:37]([CH:38]=[O:39])=[CH:36][C:35]=1[C:42]([F:45])([F:44])[F:43]>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:38]([C:37]2[CH:40]=[CH:41][C:34]([S:33][CH3:32])=[C:35]([C:42]([F:45])([F:44])[F:43])[CH:36]=2)[OH:39])(=[O:8])=[O:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1

Participants

6

Reactant 4

HCID 8058HexaneHCID 222736501H-Pyrrolo[2,3-B]pyridine, 5-methoxy-1-(phenylsulfonyl)-HCID 59234010Benzaldehyde, 4-(methylthio)-3-(trifluoromethyl)-HCID 178418339Butyllithium

Product 1

HCID 67229413(1-benzenesulfonyl-5-methoxy-1H-pyrrolo[2,3-b]pyridin-2-yl)-(4-methylsulfanyl-3-trifluoromethyl-phenyl)-methanolYield 91%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a −78° C. suspension of 1-benzenesulfonyl-5-methoxy-1H-pyrrolo[2,3-b]pyridine (3.17 g, 11 mmol) in dry tetrahydrofuran (50 mL) was added n-butyllithium in n-hexane (1.6 M, 6.9 mL, 11 mmol) dropwise. The mixture was stirred at −78° C. for 30 min before adding 4-methylsulfanyl-3-trifluoromethyl-benzaldehyde (2.65 g, 12 mmol) dropwise. The resulting mixture was stirred at −78° C. for 1 h and quenched by adding brine (20 mL). The mixture was extracted with ethyl acetate (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) (20% ethyl acetate/hexanes) afforded (1-benzenesulfonyl-5-methoxy-1H-pyrrolo[2,3-b]pyridin-2-yl)-(4-methylsulfanyl-3-trifluoromethyl-phenyl)-methanol as colorless oil (5.08 g, 91%): LC/MS m/e calcd for C23H20F3N2O4S2 [M+H]+ 509.07, observed 509.0.

Workup

  1. stirringThe resulting mixture was stirred at −78° C. for 1 h
  2. customquenched
  3. additionby adding brine (20 mL)
  4. extractionThe mixture was extracted with ethyl acetate (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) (20% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-a0fe08e3314d4b19bc9ff213cb5e727d
Source dataset
uspto-grants-2012_07
Patent number
US08222416B2

Reaction notes

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