Potassium Carbonate → 6-(1-Hydroxy-1,3-dihydro-benzo[c][1,2]oxaborol-5-yloxy)-2-isopropoxy-nicotinonitrile

HRID 1664441Notes

Reaction equation

Cl[C:2]1[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:10][CH2:11][CH2:12]C)[N:3]=1.[B:14]1([OH:24])[C:18]2[CH:19]=[CH:20][C:21]([OH:23])=[CH:22][C:17]=2[CH2:16][O:15]1.[C:25](=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[OH:24][B:14]1[C:18]2[CH:19]=[CH:20][C:21]([O:23][C:2]3[CH:9]=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:10][CH:11]([CH3:12])[CH3:25])[N:3]=3)=[CH:22][C:17]=2[CH2:16][O:15]1

Participants

Conditions

Temperature: 95 °C

Procedure

To a mixture of 6-chloro-2-propoxy-nicotinonitrile (0.54 g, 3.0 mmol) and 3H-benzo[c][1,2]oxaborole-1,5-diol (0.40 g, 2.0 mmol) in DMF (10 mL) was added potassium carbonate (0.83 g, 6.0 mmol). The resulting suspension was heated at 95° C. for 48 h. DMF was removed under reduced pressure, the residue was diluted with EtOAc (50 mL), washed with water (10 mL) and brine (2×10 mL), dried over Na2SO4, filtered, and concentrated to give brown oil. Purification was accomplished by reverse phase preparative HPLC using MeOH/H2O (0.1% AcOH) as the eluent to yield the title compound (0.25 g, 26%) as a white solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.25 (s, 1H), 8.24 (d, J=8.2 Hz, 1H), 7.79 (d, J=7.8 Hz, 1H), 7.29 (s, 1H), 7.17-7.22 (m, 1H), 6.69 (d, J=8.6 Hz, 1H), 4.99 (s, 2H), 4.07 (t, J=6.8 Hz, 2H), 1.65-1.55 (m, 2H), 0.81 (t, J=7.4 Hz, 3H); MS (ES) m/z: 311 (M+1)+; HPLC purity 98.36% (Maxplot), 97.66% (220 nm).

Workup

customDMF was removed under reduced pressure
additionthe residue was diluted with EtOAc (50 mL)
washwashed with water (10 mL) and brine (2×10 mL)
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated
customto give brown oil
customPurification

Sources & evidence

ORD record: ord-76966bda2d314fe886bdf11aa8da9d11
Source dataset: uspto-grants-2011_10
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08039450B2

Reaction notes

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