Water → HCID 66726482, compound

HRID 2284511Notes

Reaction equation

HRID 2284511 reaction equation
Cl[C:2]1[C:9]([C:10]([F:13])([F:12])[F:11])=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:14][CH2:15][CH2:16][O:17][CH:18]([CH3:20])[CH3:19])[N:3]=1.[B:21]1([OH:31])[C:25]2[CH:26]=[CH:27][C:28]([OH:30])=[CH:29][C:24]=2[CH2:23][O:22]1.C([O-])([O-])=O.[Cs+].[Cs+].O>CS(C)=O>[OH:31][B:21]1[C:25]2[CH:26]=[CH:27][C:28]([O:30][C:2]3[C:9]([C:10]([F:13])([F:12])[F:11])=[CH:8][C:5]([C:6]#[N:7])=[C:4]([O:14][CH2:15][CH2:16][O:17][CH:18]([CH3:20])[CH3:19])[N:3]=3)=[CH:29][C:24]=2[CH2:23][O:22]1

Participants

6

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 579686991,3-Dihydro-1-hydroxy-2,1-benzoxaborol-5-olHCID 86661734HCID 86661734, compound

Product 1

HCID 66726482HCID 66726482, compoundYield 69.4%

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent

Conditions

Temperature
40 °C

Procedure

A mixture of 6-chloro-2-(2-isopropoxyethoxy)-5-(trifluoromethyl)nicotinonitrile (180 mg, 0.58 mmol), benzo[c][1,2]oxaborole-1,5(3H)-diol (87 mg, 0.58 mmol) and Cs2CO3 (228 mg, 0.7 mmol) in DMSO (20 mL) was stirred at 40° C. for 1 hr, the mixture was diluted by water, extracted by EtOAc, the organic layer was concentrated in vacuo and the residue was purified by prep. HPLC (column: Gemini 100×21.2 mm, 5 g; liquid phase: [A-H2O; B—CH3CN+0.4% NH4OH] B %:45%-65%, 15 min) to afford 6-(1-hydroxy-1,3-dihydrobenzo[c][1,2]oxaborol-5-yloxy)-2-(2-isopropoxyethoxy)-5-(trifluoromethyl)nicotinonitrile (170 mg, 69%). 1H-NMR (400 MHz, DMSO-d6) δ (ppm) 9.24 (s, 1H), 8.73 (s, 1H), 7.79-7.77 (d, 1H), 7.31-7.31 (d, 1H), 7.23-7.21 (q, 1H), 4.97 (s, 2H), 4.14-4.11 (t, 2H), 3.47-3.45 (t, 2H), 3.43-3.37 (m, 1H), 0.98-0.96 (d, 6H).

Workup

  1. extractionextracted by EtOAc
  2. concentrationthe organic layer was concentrated in vacuo
  3. customthe residue was purified by prep

Sources & evidence

ORD record
ord-aceab664b999472caf417c47b8aedfdb
Source dataset
uspto-grants-2015_09
Patent number
US09145429B2

Reaction notes

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