Ethyl Bromide → ethyl 6-chloro-5-ethoxy-2-(trifluoromethyl)-2H-chromene-3-carboxylate

HRID 855143Notes

Reaction equation

HRID 855143 reaction equation
[Cl:1][C:2]1[C:3]([OH:19])=[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]([OH:18])=[O:17])=[CH:5]2.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:26](Br)[CH3:27].[C:29](OCC)(=O)[CH3:30]>CN(C=O)C>[Cl:1][C:2]1[C:3]([O:19][CH2:26][CH3:27])=[C:4]2[C:9](=[CH:10][CH:11]=1)[O:8][CH:7]([C:12]([F:15])([F:13])[F:14])[C:6]([C:16]([O:18][CH2:29][CH3:30])=[O:17])=[CH:5]2

Participants

6

Reactant 4

HCID 6332Ethyl BromideHCID 8857Ethyl AcetateHCID 10796Cesium carbonateHCID 589344716-chloro-5-hydroxvl-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid

Product 1

HCID 58934927ethyl 6-chloro-5-ethoxy-2-(trifluoromethyl)-2H-chromene-3-carboxylate

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To the mixture of 6-chloro-5-hydroxyl-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid (0.5g, 1.7 mmol) and cesium carbonate (800 mg, 0.94 mmol) in 10 mL of DMF was added ethyl bromide(0.80 mnL, 6.2 mmol). The mixture was stirred at room temperature overnight. To the reaction was added 150 mL of ethyl acetate, the resulting organic solution was washed with brine, and dried over anhydrous magnesium sulfate. After removing the volatiles, the residue was purified on silica gel column with EtOAc/hexane mixture. It gave 0.4 g of white solid. Part of the product was further purified on reverse phase HPLC for analytical characterization. LC-MS(ES+) 351.3(M+1, 100), 19F NMR(CDCl3/400 Hz) −78.782(d, J=6.8 Hz); 1H NMR (CDCl3/400 Hz) 7.94(s, 1H), 7.27(d, J=8.8 Hz, 1H), 6.70(d, J=8.8 Hz, 1H), 5.66(q, J=6.8 Hz, 1H), 4.32(m, 2H), 4.10(m, 2H), 1.42(t, J=7.2 Hz, 3H), 1.34(t, J=7.2 Hz, 3H); 13C NMR(CDCl3/400 Hz) 163.8, 153.2, 152.6, 133.5, 132.0, 123.5(q, J=287.6 Hz), 121.2, 117.2, 115.6, 112.6, 71.4, 70.5(q, J=33.2 Hz), 61.8, 15.5, 14.4. High resolution MS(ES+) m/e calc. for C15H15ClF3O4: 351.0605(M+H), 351.0641(M+H, observed).

Workup

  1. washthe resulting organic solution was washed with brine
  2. dry with materialdried over anhydrous magnesium sulfate
  3. customAfter removing the volatiles
  4. customthe residue was purified on silica gel column with EtOAc/hexane mixture

Sources & evidence

ORD record
ord-70d0c2e370de4e5195978c8c21b20524
Source dataset
uspto-grants-2007_08
Patent number
US07259266B2

Reaction notes

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