Potassium Phosphate, Tribasic → HCID 59596239, compound

HRID 2264713Notes

Reaction equation

HRID 2264713 reaction equation
[C:1]([O:5][C:6]([NH:8][C:9]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([C:26]2[CH:27]=[CH:28][C:29]([O:40]S(C(F)(F)F)(=O)=O)=[C:30]([C:32]3[CH:37]=[CH:36][CH:35]=[C:34]([O:38][CH3:39])[CH:33]=3)[CH:31]=2)([C:18]2[CH:23]=[CH:22][C:21]([O:24][CH3:25])=[CH:20][CH:19]=2)[N:10]=1)=[O:7])([CH3:4])([CH3:3])[CH3:2].P([O-])([O-])([O-])=O.[K+].[K+].[K+].COC1C=C(B(O)O)C=CC=1.COCCOC.O.C(O)C>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(OCC)(=O)C>[C:1]([O:5][C:6](=[O:7])[NH:8][C:9]1[C:17]2[C:12](=[CH:13][CH:14]=[CH:15][CH:16]=2)[C:11]([C:26]2[CH:31]=[C:30]([C:32]3[CH:37]=[CH:36][CH:35]=[C:34]([O:38][CH3:39])[CH:33]=3)[C:29]([OH:40])=[CH:28][CH:27]=2)([C:18]2[CH:19]=[CH:20][C:21]([O:24][CH3:25])=[CH:22][CH:23]=2)[N:10]=1)([CH3:4])([CH3:3])[CH3:2]

Participants

7

Reactant 4

HCID 62657Potassium Phosphate, TribasicHCID 2734370(3-Methoxyphenyl)boronic acid2×HCID 59596278HCID 59596278, compoundHCID 86587095Dimethoxyethane ethanol water

Product 1

HCID 59596239HCID 59596239, compound

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalyst2×HCID 8857Ethyl AcetateSolvent

Procedure

To [3-(3-bromo-4-hydroxy-phenyl)-3-(4-methoxy-phenyl)-3H-isoindol-1-yl]-carbamic acid tert-butyl ester (Scheme #2, E) (364 mg, 0.72 mmol) was added potassium phosphate (303 mg, 1.43 mmol), 3-methoxyphenylboronic acid (163 mg, 1.07 mmol), dichlorobis(triphenylphosphine)palladium(II) (50 mg, 0.072 mmol), and 1,2-dimethoxyethane: water:ethanol (7:3:2, 20 mL). The reaction was placed in a hot bath and heated to reflux. After 10 minutes additional 3-methoxyphenylboronic acid (60 mg) and dichlorobis(triphenylphosphine)palladium(II) (25 mg) were added and the reaction refluxed for 30 minutes. Ethyl acetate was added, salts filtered off, and the filtrate removed of solvent under reduced pressure. The mixture was purified three times; first using 20 g silica eluting with 5% acetone/dichloromethane, second using 20 g silica eluting with dichloromethane then 5% acetone/dichloromethane, and third using 40 g silica eluting with a gradient of hexanes to 50% ethyl acetate/hexanes. The product was removed of solvent under reduced pressure to give the title compounds as a white solid which was placed under high vacuum over night (208 mg, 54%). 1H NMR (300 MHz, DMSO-d6-/TFA-d) δ 8.62 (d, J=7.9 Hz, 1 H), 7.88 (t, J=7.6 Hz, 1 H), 7.78-7.69 (m, 2 H), 7.34-7.29 (m, 4 H), 7.10-7.02 (m, 3 H), 6.95-6.86 (m, 4 H), 3.76 (d, J=2.1 Hz, 6 H), 1.62 (s, 9 H); MS (APCI+) m/z 537 [M+1]+; tR=2.50 min.

Workup

  1. customThe reaction was placed in a hot bath
  2. temperatureheated to reflux
  3. temperaturethe reaction refluxed for 30 minutes
  4. filtrationsalts filtered off
  5. customthe filtrate removed of solvent under reduced pressure
  6. customThe mixture was purified three times
  7. customThe product was removed of solvent under reduced pressure

Sources & evidence

ORD record
ord-5f8c16b1ef314db9823a715c8ca9c057
Source dataset
uspto-grants-2010_12
Patent number
US07855213B2

Reaction notes

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