Ethanol → 4-Ethoxy-1-methyl-5-pyridin-3-yl-1,3-dihydro-indol-2-one

HRID 1623557Notes

Reaction equation

HRID 1623557 reaction equation
[OH:1][C:2]1[C:10]([C:11]2[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=2)=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][C:5](=[O:18])[N:6]2[CH3:17].[C:19]1(C)C=CC=C[CH:20]=1.C(O)C.C(C=P(CCCC)(CCCC)CCCC)#N>ClCCl.[Cl-].[Na+].O>[CH2:19]([O:1][C:2]1[C:10]([C:11]2[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=2)=[CH:9][CH:8]=[C:7]2[C:3]=1[CH2:4][C:5](=[O:18])[N:6]2[CH3:17])[CH3:20]

Participants

7

Reactant 4

HCID 702EthanolHCID 1140TolueneHCID 4622928CyanomethylenetributylphosphoraneHCID 667938964-Hydroxy-1-methyl-5-pyridin-3-yl-1,3-dihydro-indol-2-one

Product 1

HCID 667890244-Ethoxy-1-methyl-5-pyridin-3-yl-1,3-dihydro-indol-2-one

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 57417360Sodium chloride; waterSolvent

Conditions

Temperature
105 °C

Procedure

A microwavable vial was charged with 4-hydroxy-1-methyl-5-pyridin-3-yl-1,3-dihydro-indol-2-one (48.1 mg, 0.2 mmol), toluene (2 ml), and ethanol (23.3 μL, 0.4 mmol). Cyanomethylene-tri-n-butylphosphorane (CAS#157141-27-0, 169 mg, 0.700 mmol) was then added to the vial. The reaction vial was sealed and was heated by microwave irradiation at 105° C. for 1 hour. The reaction mixture was cooled to room temperature and diluted with dichloromethane and brine. The layers were separated and the aqueous layer was extracted an additional two times with dichloromethane. The organic layers were combined dried over anhydrous sodium sulfate, filtered and concentrated. The resulting residue was purified by silica gel flash chromatography (ethyl acetate-heptane, 0 to 100%). Further purification was accomplished via reverse phase HPLC (10 to 40% acetonitrile/water w/0.1% NH4OH) to afford 4-ethoxy-1-methyl-5-pyridin-3-yl-1,3-dihydro-indol-2-one; HRMS: (ESI) m/z 269.1289 (M+H)+, 1H NMR (400 MHz, CD2Cl2) δ ppm 1.16 (t, J=6.95 Hz, 3H), 3.20 (s, 3H), 3.60 (s, 2H), 3.85 (q, J=6.91 Hz, 2H), 6.68 (d, J=8.08 Hz, 1H), 7.28 (d, J=8.08 Hz, 1H), 7.32 (dd, J=7.83, 4.80 Hz, 1H), 7.85 (dt, J=7.89, 1.99 Hz, 1H), 8.51 (dd. J4.80, 1.77 Hz, 1H), 8.71 (d, J=2.78 Hz, 1H).

Workup

  1. customThe reaction
  2. customvial was sealed
  3. temperatureThe reaction mixture was cooled to room temperature
  4. customThe layers were separated
  5. extractionthe aqueous layer was extracted an additional two times with dichloromethane
  6. dry with materialThe organic layers were combined dried over anhydrous sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe resulting residue was purified by silica gel flash chromatography (ethyl acetate-heptane, 0 to 100%)
  10. customFurther purification

Sources & evidence

ORD record
ord-f6917d218a914bd69bb5b7eaa581a152
Source dataset
uspto-grants-2014_07
Patent number
US08778972B2

Reaction notes

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