Dimethyl[5-(benzyloxy)-1-(biphenyl-3-yl)-4-oxo-1,4-dihydropyridin-3-yl]boronate → [1-(Biphenyl-3-yl)-5-hydroxy-4-oxo-1,4-dihydropyridin-3-yl]boronic acid

HRID 1056887Notes

Reaction equation

HRID 1056887 reaction equation
C[O:2][B:3]([C:6]1[C:11](=[O:12])[C:10]([O:13]CC2C=CC=CC=2)=[CH:9][N:8]([C:21]2[CH:22]=[C:23]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[CH:24]=[CH:25][CH:26]=2)[CH:7]=1)[O:4]C>C1COCC1.CO.CO.[Pd]>[C:23]1([C:27]2[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=2)[CH:24]=[CH:25][CH:26]=[C:21]([N:8]2[CH:9]=[C:10]([OH:13])[C:11](=[O:12])[C:6]([B:3]([OH:2])[OH:4])=[CH:7]2)[CH:22]=1

Participants

5

Reactant 1

HCID 67404775Dimethyl[5-(benzyloxy)-1-(biphenyl-3-yl)-4-oxo-1,4-dihydropyridin-3-yl]boronate

Product 1

HCID 53379376[1-(Biphenyl-3-yl)-5-hydroxy-4-oxo-1,4-dihydropyridin-3-yl]boronic acid

Reagents, catalysts & solvents 3

HCID 23938PalladiumCatalystHCID 887MethanolSolventHCID 21899815MeOH tetrahydrofuranSolvent

Procedure

The solution of crude dimethyl[5-(benzyloxy)-1-(biphenyl-3-yl)-4-oxo-1,4-dihydropyridin-3-yl]boronate (2.4 mmol) in THF/MeOH from the preceeding step and 10% Pd/C (52 mg, 0.49 mmol) was stirred under H2 (1 atm) for 18 h. The reaction mixture was diluted with MeOH (20 mL), filtered through a pad of Celite (MeOH wash), and concentrated under reduced pressure, The residue was diluted with DMF (10 mL) and 0.5 M aq, HCl (0.4 mL) and purified by reversed phase HPLC (2 cm×5 cm C18, acetonitrile-water gradient, 0.05% TFA added, fractions were lyopholized) to provide [1-(biphenyl-3-yl)-5-hydroxy-4-oxo-1,4-dihydropyridin-3-yl]boronic acid. ′H NMR (599 MHz, DMSO, 75° C.): S 8.19 (d, J=2.3 Hz, 1H); 7.89 (d, J=2.3 Hz, 1H); 7.83 (s, 1H); 7.79-7.74 (m, 3H); 7.67-7.61 (m, 1H); 7.56 (d, J=8.1 Hz, 1H); 7.49 (t, J Hz, 2H); 7.46-7.38 (m, 1H). HRMS (ES) calc (M+H)+ −308.1089. found 308.1092.

Workup

  1. filtrationfiltered through a pad of Celite (MeOH wash)
  2. concentrationconcentrated under reduced pressure
  3. additionThe residue was diluted with DMF (10 mL) and 0.5 M aq
  4. customHCl (0.4 mL) and purified by reversed phase HPLC (2 cm×5 cm C18, acetonitrile-water gradient, 0.05% TFA added, fractions were lyopholized)

Sources & evidence

ORD record
ord-46068a0e799c4c7890e94250f4ddf355
Source dataset
uspto-grants-2016_07
Patent number
US09399651B2

Reaction notes

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