Potassium Carbonate → 5-Fluoro-2-(3-methyl-benzo[d]isoxazol-6-yloxy)-benzonitrile

HRID 1715598Notes

Reaction equation

[CH3:1][C:2]1[C:6]2[CH:7]=[CH:8][C:9]([OH:11])=[CH:10][C:5]=2[O:4][N:3]=1.F[C:13]1[CH:20]=[CH:19][C:18]([F:21])=[CH:17][C:14]=1[C:15]#[N:16].C(=O)([O-])[O-].[K+].[K+]>CC(N(C)C)=O.CCOC(C)=O>[F:21][C:18]1[CH:19]=[CH:20][C:13]([O:11][C:9]2[CH:8]=[CH:7][C:6]3[C:2]([CH3:1])=[N:3][O:4][C:5]=3[CH:10]=2)=[C:14]([CH:17]=1)[C:15]#[N:16]

Participants

Conditions

Temperature: 100 °C

Procedure

3-Methyl-benzo[d]isoxazol-6-ol (1v) (reference for synthesis, see Indian J. Chem. Sect. B; 19:571-575 (1980)) (1.58 g, 10.6 mmol) and 2,5-difluoro-benzonitrile (2v) (1.47 g, 10.6 mmol) were combined with potassium carbonate (1.46 g. 10.6 mmol) in 15 mL of dry DMA. The reaction was heated in a 100° C. bath for 6 hours. The reaction was cooled and diluted with EtOAc (200 mL) and washed three times with water, NH4Cl, NaHCO3, and brine. The organic solution was dried over MgSO4 and concentrated. The crude residue was purified by column chromatography (silica, 70-80% CH2Cl2/hexane) to provide compound (3v) (1.65 g, 58% yield). 1H NMR (400 MHz, CDCl3) δ 7.63 (d, J=8.6 Hz, 1H), 7.44-7.41 (m, 1H), 7.33-7.26 (m, 1H), 7.10-7.06 (m, 2H), 7.03 (dd, J=8.2, 4.7 Hz, 1H), 2.59 (s, 3H); MS (ESI+) m/z 269 (M+H) detected.

Workup

temperatureThe reaction was cooled
washwashed three times with water, NH4Cl, NaHCO3, and brine
dry with materialThe organic solution was dried over MgSO4
concentrationconcentrated
customThe crude residue was purified by column chromatography (silica, 70-80% CH2Cl2/hexane)

Sources & evidence

ORD record: ord-bf6eb57fc41347e0a64b241c538e841b
Source dataset: uspto-grants-2010_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07799782B2

Reaction notes

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