Phenol → ethyl 6-chloro-5-phenoxy-2-(trifluoromethyl)-2H-chromene-3-carboxylate

HRID 855034Notes

Reaction equation

[Cl:1][C:2]1[C:3](F)=[C:4]2[C:9](=[CH:10][CH:11]=1)[O:8][CH:7]([C:12]([F:15])([F:14])[F:13])[C:6]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:5]2.[C:22]1([OH:28])[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=1.C(=O)([O-])[O-].[K+].[K+].CC#N>CN(C=O)C.O>[Cl:1][C:2]1[C:3]([O:28][C:22]2[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=2)=[C:4]2[C:9](=[CH:10][CH:11]=1)[O:8][CH:7]([C:12]([F:15])([F:14])[F:13])[C:6]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:5]2

Participants

Conditions

Temperature: 110 °C

Procedure

To 162.3 g (0.5 mmole) of ethyl 6-chloro-5-fluoro-2-(trifluoromethyl)-2H-chromene-3-carboxylate was added 75 mg (0.80 mmole) of phenol and 120 mg (0.87 mmole) of potassium carbonate in 1.5 mL DMF. The mixture was heated to 110° C. and allowed to stir overnight. After cooling, the mixture was diluted with water and extracted three times with diethyl ether. The combined organic fractions were washed with water, dried and concd to give a crude oil. Preparative reverse phase chromatography (C 18, 4.0 cm×25 cm column, gradient 50%-100% CH3CN) afforded 50 mg (25.1%) of a clear, colorless oil: 1H NMR (CDCl3/400 MHz) 1.28 (t, 3H, J=7.1 Hz), 4.26 (m, 2H), 5.70 (q, 1H, J=6.7 Hz), 6.82 (d, 2H, J=7.9 Hz), 6.87 (d, 1H, J=8.7 Hz), 7.06 (t, 1H, J=7.4 Hz), 7.31 (t, 2H, J=8.1 Hz), 7.38 (d, 1H, J=8.9 Hz), 7.79 (s, 1H); 19F NMR (CDCl3/400 MHz) −78.7 (d, 3F, 6.8 Hz); MS (ESI+) 399 (M+1, 100); MS (EI) 398 (M+, 50), 329 (100), 283 (79), 231 (32); HRMS (EI) m/z calcd for (C19H14O4ClF3) 398.0533, found 398.0538.

Workup

temperatureAfter cooling
extractionextracted three times with diethyl ether
washThe combined organic fractions were washed with water
customdried
customto give a crude oil

Sources & evidence

ORD record: ord-6b3bdeae1c3941afb67e456e5ed89848
Source dataset: uspto-grants-2007_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07259266B2

Reaction notes

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