1,2-Dimethoxyethane → 4-Benzyloxy-1-methyl-5-pyridin-3-yl-1,3-dihydro-indol-2-one

HRID 1623555Notes

Reaction equation

HRID 1623555 reaction equation
[CH2:1]([O:8][C:9]1[C:17](Br)=[CH:16][CH:15]=[C:14]2[C:10]=1[CH2:11][C:12](=[O:20])[N:13]2[CH3:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[N:21]1[CH:26]=[CH:25][CH:24]=[C:23](B(O)O)[CH:22]=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>[CH2:1]([O:8][C:9]1[C:17]([C:23]2[CH:22]=[N:21][CH:26]=[CH:25][CH:24]=2)=[CH:16][CH:15]=[C:14]2[C:10]=1[CH2:11][C:12](=[O:20])[N:13]2[CH3:19])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 27343783-Pyridinylboronic acidHCID 667884774-Benzyloxy-5-bromo-1-methyl-1,3-dihydro-indol-2-one

Product 1

HCID 667877154-Benzyloxy-1-methyl-5-pyridin-3-yl-1,3-dihydro-indol-2-one

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 6344DichloromethaneSolvent

Conditions

Temperature
130 °C

Procedure

To 4-benzyloxy-5-bromo-1-methyl-1,3-dihydro-indol-2-one (100 mg, 0.301 mmol) was added 3-pyridineboronic acid (CAS#1692.25-7, 44.4 mg, 0.361 mmol), 1,2-dimethoxyethane (2 mL) and 2 M aqueous sodium carbonate (0.376 ml, 0.753 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, (82 mg, 0.0093 mmol)] was added. The reaction vessel was sealed and was heated by microwave irradiation at 130° C. for 2.5 hours. The reaction mixture was 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 purified by silica gel flash chromatography (ethyl acetate-dichloromethane, 0 to 100%) to afford 4-benzyloxy-1-methyl-5-pyridin-3-yl-1,3-dihydro-indol-2-one; HRMS: (ESI) m/z 331.1447 (M+H)+; 1H NMR (400 MHz, DMSO-d6) δ ppm 3.16 (s, 3H), 3.77 (s 2H), 4.93 (s, 2H), 6.88 (d J=8.08 Hz, 1H), 7.16-7.21 (m, 2H), 7.27-7.31 (m, 3H), 7.35 (d, J=8.08 Hz, 1H), 7.41 (qd, 1H), 7.86 (dt, J=7.83, 2.02 Hz, 1H), 5.52 (dd, J=4.80, 1.77 Hz, 1H), 8.67 (dd, J=2.27, 0.76 Hz, 1H).

Workup

  1. customThe reaction mixture was degassed
  2. additionwas added
  3. customThe reaction vessel was sealed
  4. temperatureThe reaction mixture was 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 purified by silica gel flash chromatography (ethyl acetate-dichloromethane, 0 to 100%)

Sources & evidence

ORD record
ord-64ae905fe99046f5ae5fadb3e4cde353
Source dataset
uspto-grants-2014_07
Patent number
US08778972B2

Reaction notes

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