3-Nitrophenylboronic Acid → HCID 58019948, compound

HRID 1632087Notes

Reaction equation

HRID 1632087 reaction equation
Br[C:2]1[CH:3]=[C:4]([CH2:10][CH2:11][N:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]2=[O:18])[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].[N+:19]([C:22]1[CH:23]=[C:24](B(O)O)[CH:25]=[CH:26][CH:27]=1)([O-:21])=[O:20].C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[K+].[K+]>CCOCC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O.C(O)C.C(COC)OC>[CH3:9][O:8][C:7]1[C:2]([C:26]2[CH:25]=[CH:24][CH:23]=[C:22]([N+:19]([O-:21])=[O:20])[CH:27]=2)=[CH:3][C:4]([CH2:10][CH2:11][N:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]2=[O:18])=[CH:5][CH:6]=1

Participants

10

Reactant 4

HCID 16773-Nitrophenylboronic AcidHCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 58020135HCID 58020135, compound

Product 1

HCID 58019948HCID 58019948, compoundYield 31.1%

Reagents, catalysts & solvents 5

HCID 167845palladium(II) acetateCatalystHCID 702EthanolSolventHCID 962WaterSolventHCID 3283Diethyl EtherSolventHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
80 °C

Procedure

Into a 40 mL vial were added 1-[2-(3-bromo-4-methoxy-phenyl)-ethyl]-1H-pyridin-2-one (I-166, 210 mg, 0.68 mmol), 3-nitrophenylboronic acid (125 mg, 0.75 mmol), PPh3 (36 mg, 0.014 mmol), potassium carbonate (283 mg, 2.04 mmol), dimethoxyethane (10 mL), ethanol (1 mL), and water (1 mL). The suspension was degassed with N2 for 5 minutes and then palladium(II) acetate (15 mg, 0.068 mmol). After degassing for an additional 2 minutes the reaction was stirred at 80° C. for 18 hours. To the reaction was added 5 mL of water and 10 mL of ethyl acetate. The layers were separated and the aqueous was extracted with ethyl acetate (3×10 mL). The organics were combined and concentrated. The residue was purified by flash column chromatography eluting with 10-20% acetone/dichloromethane. The yellow oil which was obtained (136 mg) was dissolved in 1 mL of ether and allowed to stand at room temperature for 3 days. The tan solid which formed was filtered, washed with ether, and dried to afford 74 mg of P-244 in 31% yield. 1H NMR (400 MHz, CDCl3) δ 8.30-8.29 (m, 1H), 8.18-8.15 (m, 1H), 7.81-7.79 (m, 1H), 7.54 (t, J=8.0 Hz), 7.37-7.33 (m, 1H), 7.19 (dd, J=8.2, 2.2 Hz, 1H), 7.05 (d, J=2.4 Hz, 1H), 6.95-6.93 (m, 2H), 6.61 (d, J=9.2 Hz, 1H), 6.06 (td, J=6.6, 1.2 Hz, 1H), 4.15 (t, J=7.0 Hz, 2H), 3.82 (s, 3H), 3.07 (t, J=7.0 Hz, 2H) ppm. LC/MS=99.4%, 351.6 (ESI+).

Workup

  1. customThe suspension was degassed with N2 for 5 minutes
  2. customAfter degassing for an additional 2 minutes the reaction
  3. additionTo the reaction was added 5 mL of water and 10 mL of ethyl acetate
  4. customThe layers were separated
  5. extractionthe aqueous was extracted with ethyl acetate (3×10 mL)
  6. concentrationconcentrated
  7. customThe residue was purified by flash column chromatography
  8. washeluting with 10-20% acetone/dichloromethane
  9. customThe yellow oil which was obtained (136 mg)
  10. waitto stand at room temperature for 3 days
  11. customThe tan solid which formed
  12. filtrationwas filtered
  13. washwashed with ether
  14. customdried

Sources & evidence

ORD record
ord-8eca9d15ec064b35876475a9b09b62cb
Source dataset
uspto-grants-2014_07
Patent number
US08791267B2

Reaction notes

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