Cesium carbonate → 6-(1-Hydroxy-1,3-dihydro-benzo[c][1,2]oxaborol-5-yloxy)-5-methoxymethoxy-nicotinonitrile

HRID 1471582

Reaction equation

Cl[C:2]1[C:9]([O:10][CH2:11][O:12][CH3:13])=[CH:8][C:5]([C:6]#[N:7])=[CH:4][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(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[OH:24][B:14]1[C:18]2[CH:19]=[CH:20][C:21]([O:23][C:2]3[C:9]([O:10][CH2:11][O:12][CH3:13])=[CH:8][C:5]([C:6]#[N:7])=[CH:4][N:3]=3)=[CH:22][C:17]=2[CH2:16][O:15]1

Participants

Conditions

Temperature: 80 °C

Procedure

To a mixture of 6-chloro-5-methoxymethoxy-nicotinonitrile (0.68 g, 3.42 mmol) and 3H-benzo[c][1,2]oxaborole-1,5-diol (0.56 g, 3.76 mmol) in DMF (10 mL) was added cesium carbonate (2.45 g, 7.52 mmol). The resulting suspension was heated at 80° C. for overnight. DMF was removed under reduced pressure, the residue was diluted with EtOAc (50 mL), washed with water (10 mL) and brine (10 mL), dried over Na2SO4, filtered, and concentrated to give brown oil. Purification was accomplished by flash chromatography on silica gel using 1-100% MeOH/EtOAc gradient elution to yield the title compound (0.40 g, 40%) as a transparent oil. 1H NMR (400 MHz, DMSO-d6) δ ppm 9.23 (s, 1 H), 8.24 (s, 1 H), 8.03 (s, 1 H), 7.77 (d, J=8.6 Hz, 1 H), 7.23 (s, 1 H), 7.14 (d, J=7.4 Hz, 1 H), 5.40 (s, 2 H), 4.98 (s, 2 H), 3.45 (s, 3 H); MS (ES) m/z: 313 (M+1)+.

Workup

customDMF was removed under reduced pressure
additionthe residue was diluted with EtOAc (50 mL)
washwashed with water (10 mL) and brine (10 mL)
dry with materialdried over Na2SO4
filtrationfiltered
concentrationconcentrated
customto give brown oil
customPurification
washwas accomplished by flash chromatography on silica gel using 1-100% MeOH/EtOAc gradient elution

Sources & evidence

ORD record: ord-b08f5744a62e46e8ab42a99b97edbb39
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09012431B2

Linked notes

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