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

HRID 1897457Notes

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-749ecacb982c43129889d7e4aaf11433
Source dataset: uspto-grants-2013_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08518983B2

Reaction notes

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