3-(Methoxycarbonyl)benzeneboronic acid → HCID 67160183, compound

HRID 471844Notes

Reaction equation

HRID 471844 reaction equation
CC([C:5]1([N:13]([CH2:17][C:18]2[CH:23]=[CH:22][C:21](Br)=[CH:20][CH:19]=2)[C:14](=[O:16])[O-:15])[CH2:10][CH2:9][C:8]([CH3:12])([CH3:11])[CH2:7][CH2:6]1)(C)C.[CH3:25][O:26][C:27]([C:29]1[CH:30]=[C:31](B(O)O)[CH:32]=[CH:33][CH:34]=1)=[O:28]>CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:11][C:8]1([CH3:12])[CH2:9][CH2:10][CH:5]([N:13]([CH2:17][C:18]2[CH:23]=[CH:22][C:21]([C:31]3[CH:32]=[CH:33][CH:34]=[C:29]([C:27]([O:26][CH3:25])=[O:28])[CH:30]=3)=[CH:20][CH:19]=2)[C:14]([O:15][C:8]([CH3:11])([CH3:9])[CH3:7])=[O:16])[CH2:6][CH2:7]1

Participants

4

Reactant 2

HCID 27347143-(Methoxycarbonyl)benzeneboronic acidHCID 86653623HCID 86653623, compound

Product 1

HCID 67160183HCID 67160183, compound

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

A flask equipped with a septum-sealed reflux condenser was charged with 1,1-dimethylethyl[(4-bromophenyl)methyl](4,4-dimethylcyclohexyl)carbamate (0.988 g; 2.49 mmol; Example V-11), {3-[(methyloxy)carbonyl]phenyl}boronic acid (0.493 g; 2.74 mmol), Pd(OAc)2 (0.0028 g; 0.012 mmol) and 2-(2′,6′-dimethoxybiphenyl)di-cyclohexylphosphine (S-Phos; 0.010 g; 0.025 mmol) was evacuated and back-filled with N2 several times. PhMe/EtOH (4:1 v/v, 7.5 mL), and 2M Na2CO3 were added via syringe through the condenser's septum and the mixture was heated under reflux for 2 h (until consumption of the aryl bromide was observed). Upon cooling, the mixture was poured into EtOAc/water, the whole was filtered through a 0.45 μm PTFE membrane filter and the layers were separated. The aqueous layer was extracted with EtOAc, combined organics were washed (brine), dried over Na2SO4 and concentrated in vacuo. The residue was purified by flash chromatography (EtOAc/hexanes), affording the title compound as a colorless gum/syrup. 1H NMR (400 MHz, DMSO-d6) δ ppm 0.85 (s, 6H), 1.07-1.79 (m, 18H), 3.89 (s, 3H), 4.42 (br. s., 2H), 7.36 (d, J=8.03 Hz, 2H), 7.62 (t, J=7.85 Hz, 1H), 7.67 (d, J=8.03 Hz, 2H), 7.95 (t, J=6.96 Hz, 2H), 8.18 (s, 1H).

Workup

  1. customA flask equipped with a septum-sealed
  2. temperaturereflux condenser
  3. customwas evacuated
  4. additionback-filled with N2 several times
  5. additionPhMe/EtOH (4:1 v/v, 7.5 mL), and 2M Na2CO3 were added via syringe through the condenser's septum
  6. temperaturethe mixture was heated
  7. temperatureunder reflux for 2 h (
  8. customuntil consumption of the aryl bromide
  9. temperatureUpon cooling
  10. additionthe mixture was poured into EtOAc/water
  11. filtrationthe whole was filtered through a 0.45 μm PTFE membrane
  12. filtrationfilter
  13. customthe layers were separated
  14. extractionThe aqueous layer was extracted with EtOAc
  15. washcombined organics were washed (brine)
  16. dry with materialdried over Na2SO4
  17. concentrationconcentrated in vacuo
  18. customThe residue was purified by flash chromatography (EtOAc/hexanes)

Sources & evidence

ORD record
ord-69854f4bead14fea9c8b743cc50fa7a4
Source dataset
uspto-grants-2014_01
Patent number
US08633175B2

Reaction notes

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