Diethyl Ether → 1-[2-methyl-7-(2,4,6-trimethyl-phenyl)-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridin-3-yl]-butan-1-one

HRID 2113801Notes

Reaction equation

HRID 2113801 reaction equation
Br[C:2]1[N:3]([CH3:20])[N:4]=[C:5]2[C:10]=1[CH2:9][CH2:8][CH2:7][N:6]2[C:11]1[C:16]([CH3:17])=[CH:15][C:14]([CH3:18])=[CH:13][C:12]=1[CH3:19].C([Li])CCC.CCOCC.[C:31](Cl)(=[O:35])[CH2:32][CH2:33][CH3:34]>O1CCCC1.[Cl-].[Zn+2].[Cl-].[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:20][N:3]1[C:2]([C:31](=[O:35])[CH2:32][CH2:33][CH3:34])=[C:10]2[C:5]([N:6]([C:11]3[C:16]([CH3:17])=[CH:15][C:14]([CH3:18])=[CH:13][C:12]=3[CH3:19])[CH2:7][CH2:8][CH2:9]2)=[N:4]1

Participants

8

Reactant 4

HCID 3283Diethyl EtherHCID 8855Butyryl chlorideHCID 112328983-bromo-2-methyl-7-(2,4,6-trimethylphenyl)-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridineHCID 178418339Butyllithium

Product 1

HCID 598115251-[2-methyl-7-(2,4,6-trimethyl-phenyl)-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridin-3-yl]-butan-1-oneYield 41%

Reagents, catalysts & solvents 3

HCID 3007855ZincchlorideCatalystHCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-78 °C

Procedure

To a solution of 3-bromo-2-methyl-7-(2,4,6-trimethyl-phenyl)-4,5,6,7-tetrahydro-2H-pyrazolo [3,4-b]pyridine (0.053 g, 0.159 mmol) in 1 mL of tetrahydrofuran at −78° C. was added n-butyl lithium (0.12 mL, 0.19 mmol), and the yellow solution was stirred at −78° C. for 10 min. A 1.0 M zinc chloride in ether solution (0.45 mL, 0.45 mmol) was added, the resulting cloudy pale orange solution was stirred at RT for 10 min., then butyryl chloride (0.020 mL, 0.19 mmol) and tetrakis(triphenylphosphine) palladium(0) (0.003 g, 0.003 mmol) were added. The golden yellow solution was stirred for 3 h, then quenched with 1 mL of a saturated aqueous ammonium chloride solution. The mixture was partitioned between 5 mL of water and 5 mL of dichloromethane. The aqueous layer was extracted with 5 mL of dichloromethane, and the combined organic layers were dried over MgSO4, filtered, and concentrated to a yellow oil. Column chromatography (0→20% EtOAc/hexanes) afforded 0.021 g (41%) of 1-[2-methyl-7-(2,4,6-trimethyl-phenyl)-4,5,6,7-tetrahydro-2H-pyrazolo[3,4-b]pyridin-3-yl]-butan-1-one as a slightly impure pale yellow oil that was used without further purification.

Workup

  1. stirringthe resulting cloudy pale orange solution was stirred at RT for 10 min.
  2. stirringThe golden yellow solution was stirred for 3 h
  3. customquenched with 1 mL of a saturated aqueous ammonium chloride solution
  4. customThe mixture was partitioned between 5 mL of water and 5 mL of dichloromethane
  5. extractionThe aqueous layer was extracted with 5 mL of dichloromethane
  6. dry with materialthe combined organic layers were dried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated to a yellow oil

Sources & evidence

ORD record
ord-794806a224fa46c29fd93b00298562af
Source dataset
uspto-grants-2008_10
Patent number
US07432283B2

Reaction notes

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