1,2-Dimethoxyethane → HCID 66793981, compound

HRID 1623540Notes

Reaction equation

HRID 1623540 reaction equation
[CH3:1][O:2][C:3]1[C:11](B2OC(C)(C)C(C)(C)O2)=[CH:10][CH:9]=[C:8]2[C:4]=1[CH2:5][C:6](=[O:22])[N:7]2[CH3:21].Br[C:24]1[CH:25]=[C:26]([CH2:30][OH:31])[CH:27]=[N:28][CH:29]=1.COCCOC.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[OH:31][CH2:30][C:26]1[CH:25]=[C:24]([C:11]2[C:3]([O:2][CH3:1])=[C:4]3[C:8](=[CH:9][CH:10]=2)[N:7]([CH3:21])[C:6](=[O:22])[CH2:5]3)[CH:29]=[N:28][CH:27]=1

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 2784733(5-Bromo-3-pyridinyl)methanolHCID 667890071,3-Dihydro-4-methoxy-1-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2H-indol-2-one

Product 1

HCID 66793981HCID 66793981, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
120 °C

Procedure

To 4-methoxy-1-methyl-5-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1,3-dihydro-indol-2-one, prepared as described in Example 37a (80 mg, 0.264 mmol) was added (5-bromo-pyridin-3-yl)-methanol (CAS#37669-64-0, 55 mg, 0.29 mmol), 1,2-dimethoxyethane (3.0 mL), and 2 M aqueous sodium carbonate (0.330 mL, 066 mmol). The reaction mixture was degassed and placed under an argon atmosphere, at which time resin bound tetrakis(triphenylphosphine)palladium(0), specifically polystyrene triphenylphosphine palladium (0) [PS—PPh3-Pd(0) (Biotage), 0.11 mmol/g loading, (120 mg, 0.013 mmol)] was added. The reaction vessel was sealed and was heated by microwave irradiation at 120° C. for 3 hours. The reaction mixture was then cooled to room temperature, diluted with dichloromethane and filtered through glass wool. The filtrate was further diluted with saturated aqueous sodium bicarbonate and the layers were separated. The aqueous layer was extracted two times with dichloromethane, and the organic layers were combined, dried over anhydrous sodium sulfate, filtered and concentrated. The resulting residue was partially purified by silica gel flash chromatography (ethanol-dichloromethane, 0 to 10%). Further purification was accomplished via reverse phase HPLC (7 to 40% acetonitrile/water w/0.1% NH4OH) to furnish 5-(5-hydroxymethyl-pyridin-3-yl)-4-methoxy-1-methyl-1,3-dihydro-indol-2-one; HRMS: (ESI) m/z 285.1240 (M+H)+; 1H NMR (400 MHz, CD3OD) δ ppm 3.24 (s, 3H), 3.75 (s, 3H), 3.78 (s, 2H), 4.71 (s, 2H), 6.84 (d, J=81 Hz, 1H), 7.34 (d, J=8.1 Hz, 1H), 7.94 (d, J=2.0 Hz, 1H), 8.45 (d, J=1.8 Hz, 1H), 8.55 (d, J=2.0 Hz, 1H)

Workup

  1. customThe reaction mixture was degassed
  2. additionwas added
  3. customThe reaction vessel was sealed
  4. temperatureThe reaction mixture was then cooled to room temperature
  5. filtrationfiltered through glass wool
  6. additionThe filtrate was further diluted with saturated aqueous sodium bicarbonate
  7. customthe layers were separated
  8. extractionThe aqueous layer was extracted two times with dichloromethane
  9. dry with materialdried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customThe resulting residue was partially purified by silica gel flash chromatography (ethanol-dichloromethane, 0 to 10%)
  13. customFurther purification

Sources & evidence

ORD record
ord-141104599d924507a2ce9ada40a95969
Source dataset
uspto-grants-2014_07
Patent number
US08778972B2

Reaction notes

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