Ethyl Acetate → ethyl 7-fluoro-2-(trifluoromethyl)-2H-chromene-3-carboxylate

HRID 855132Notes

Reaction equation

HRID 855132 reaction equation
[OH:1][C:2]1[CH:9]=[C:8]([F:10])[CH:7]=[CH:6][C:3]=1[CH:4]=O.[F:11][C:12]([F:21])([F:20])/[CH:13]=[CH:14]/[C:15]([O:17][CH2:18][CH3:19])=[O:16].C(=O)([O-])[O-].[K+].[K+].C(OCC)(=O)C>CN(C)C=O>[F:10][C:8]1[CH:9]=[C:2]2[C:3]([CH:4]=[C:14]([C:15]([O:17][CH2:18][CH3:19])=[O:16])[CH:13]([C:12]([F:11])([F:21])[F:20])[O:1]2)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 8857Ethyl AcetateHCID 11430Potassium CarbonateHCID 27792684-Fluoro-2-hydroxybenzaldehydeHCID 5371261Ethyl (2E)-4,4,4-trifluoro-2-butenoate

Product 1

HCID 58934808ethyl 7-fluoro-2-(trifluoromethyl)-2H-chromene-3-carboxylateYield 60.3%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

A mixture of 2-hydroxy-4-fluorobenzaldehyde (log, 71.4 mmol), ethyl 4,4,4-trifluorocrotonate (15 mL, 100 mmol), and anhydrous potassium carbonate (14.8 g, 107.1 mmol) in 40 ml dry dimethylformamide was heated to 90° C. for five hours. LC-MS indicated that the reaction was done. After cooling to room temperature, to the reaction was added 500 mL of ethyl acetate. The organic phase was washed with brine (×3), and was then dried over anhydrous magnesium sulfate. After removing the solvent, the residue was purified on silica gel column with 1:18 EtOAc/hexane. It gave 12.5 g (60%) product as a light yellow oil. 1H NMR (CDCl3/300 MHz) 7.73(s, 1H), 7.30-7.22(m, 1H), 6.79-6.73(m, 2H), 5.76(q, J=6.9 Hz, 1H), 4.38(m, 2H), 1.37(t, J=7.2 Hz, 3H). 13C(CDCl3/300 MH) 167.2, 164.0, 163.9, 155.0(d, J=13.0 Hz), 136.3(d, J=1.28 Hz), 131.0(d, J=10.4 Hz), 123.5(q, J=287.5 Hz), 115.9(dd, J=2.4, 7.3 Hz), 110.2(d, J=22.5 Hz), 104.4(d, J=26.0 Hz), 71.0(q, J=33.2 Hz), 61.7(d, J=10.4 Hz), 14.4. 19F(CDCl3/300 MHz) −79.0(d, J=6.5 Hz), −104.8(m). LC-MS(ES+) 291.0(M+1, 100), HRMS (EI+) m/z calcd for (C13H10F4O3) 290.0566(M+), found 290.0586.

Workup

  1. temperatureAfter cooling to room temperature, to the reaction
  2. washThe organic phase was washed with brine (×3)
  3. dry with materialwas then dried over anhydrous magnesium sulfate
  4. customAfter removing the solvent
  5. customthe residue was purified on silica gel column with 1:18 EtOAc/hexane

Sources & evidence

ORD record
ord-c18286b5d7104a4faf4a7b8edfa61571
Source dataset
uspto-grants-2007_08
Patent number
US07259266B2

Reaction notes

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