Ethyl Acetate → HCID 58934475, compound

HRID 855150Notes

Reaction equation

HRID 855150 reaction equation
[F:1][C:2]1[CH:11]=[C:10]2[C:5]([CH:6]=[C:7]([C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH:8]([C:12]([F:15])([F:14])[F:13])[O:9]2)=[CH:4][CH:3]=1.[Br:21]Br.C(OCC)(=O)C>ClC(Cl)(Cl)Cl>[Br:21][C:3]1[CH:4]=[C:5]2[C:10](=[CH:11][C:2]=1[F:1])[O:9][CH:8]([C:12]([F:14])([F:15])[F:13])[C:7]([C:16]([O:18][CH2:19][CH3:20])=[O:17])=[CH:6]2

Participants

5

Reactant 3

HCID 8857Ethyl AcetateHCID 24408BromineHCID 58934808ethyl 7-fluoro-2-(trifluoromethyl)-2H-chromene-3-carboxylate

Product 1

HCID 58934475HCID 58934475, compoundYield 44.6%

Reagents, catalysts & solvents 1

HCID 5943Carbon TetrachlorideSolvent2×

Procedure

To the solution of ethyl 7-fluoro-2-(trifluoromethyl)-2H chromene-3-carboxylate (5 g, 34 mmol) in 100 mL of tetrachloromethane was added dropwise at room temperature a solution of bromine(10.5 mL, 204 mmol) in 20 mL of tetrachloromethane. The resulting solution was stirred for 24 hrs. To the reaction was added 500 mL of ethyl acetate. The resulting organic phase was then washed with aqueous sodium thiosulfite to remove excess bromine, and brine, then dried over anhydrous magnesium sulfate. After removing the volatiles, the residue was purified on silica gel column with 1:9 EtOAc/hexane. It gave 5.6 g product. A small fraction of the product was further purified on reverse phase HPLC for analytica characterization. It gave a white solid. m.p.=98.5-100.0° C. 1H NMR(CDCl3/300 MHz) 7.67(s, 1H), 7.46(d, J=7.5 Hz, 1H), 6.83(d, J=9 Hz, 1H), 5.74(q, J=6.6 Hz, 1H), 4.36(m, 2H), 1.39(t, J=7.2 Hz, 3H). 19F NMR(CDCl3/300 MHz): −78.82(d, J=6.5 Hz), −98.7(t, J=7.9 Hz). 13C NMR(CDCl3/300 MHz): 163.6, 163.1, 159.7,154.0(d, J=11.5 Hz), 135.1, 133.4, 123.4(q, J=287.3 Hz), 117.3, 105.6(d, J=26.7 Hz), 102.2(d, J=22.3 Hz), 71.1(q, J=33.3 Hz), 61.9, 14.4. LC-MS(ES+): 369.2(M+1, 100). HRMS (EI+): m/z calc. For C13H9BrF4O3: 367.9671(M+), found: 367.9675.

Workup

  1. washThe resulting organic phase was then washed with aqueous sodium thiosulfite
  2. customto remove excess bromine, and brine
  3. dry with materialdried over anhydrous magnesium sulfate
  4. customAfter removing the volatiles
  5. customthe residue was purified on silica gel column with 1:9 EtOAc/hexane

Sources & evidence

ORD record
ord-496532b3cb4f400d8c7a79d7c4050bc8
Source dataset
uspto-grants-2007_08
Patent number
US07259266B2

Reaction notes

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