Cesium carbonate → HCID 69519487, compound

HRID 854862Notes

Reaction equation

HRID 854862 reaction equation
[OH: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.F[C:22]1[CH:27]=[CH:26][C:25]([N+:28]([O-:30])=[O:29])=[CH:24][C:23]=1[F:31].C(=O)([O-])[O-].[Cs+].[Cs+]>CN(C=O)C>[F:31][C:23]1[CH:24]=[C:25]([N+:28]([O-:30])=[O:29])[CH:26]=[CH:27][C:22]=1[O: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:13])[F:14])[O:9]2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 1230531,2-Difluoro-4-nitrobenzeneHCID 69517747HCID 69517747, compound

Product 1

HCID 69519487HCID 69519487, compoundYield 84%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
90 °C

Procedure

Ethyl 7-hydroxy-2-(trifluoromethyl)-2H-chromene-3-carboxylate from Example 1a, Step 1 (0.50 g, 1.73 mmole), 1,2-difluoro-4-nitrobenzene (0.30 g, 1.91 mmole), and cesium carbonate (0.62 g, 1.91 mmole) were mixed in DMF (2 mL). Copper (I) trifluoromethanesulfonate benzene complex (5 mg) was added to above mixture. The mixture was heated to 90° C. for 6 hour. LCMS indicated product formation and there was no starting material present. The reaction was quenched with sodium bicarbonate (sat.) and extracted with ethyl acetate. The organic layer was washed with brine and dried over anhydrous MgSO4. The filtrate was evaporated and dried in vacuo to afford a brown oil, which was purified by Biotage silica chromatography with 20% ethyl acetate in hexane to provide a light yellow oil (0.62 g, 84%): LCMS m/z 449.65 (M+Na). 1NMR (CDCl3/400 MHz) 8.05 (m, 2H), 7.70 (s, 1H), 7.24 (m, 1H), 7.17 (dd, 1H, J=8.8, 8 Hz), 6.66 (m, 1H), 6 65 (s, 1H), 5.69 (q, 1H, J=6.8 Hz), 4.30 (q, 2H, J=7.2 Hz), 1.33 (t, 3H, J=7.2 Hz).

Workup

  1. additionCopper (I) trifluoromethanesulfonate benzene complex (5 mg) was added to above mixture
  2. customThe reaction was quenched with sodium bicarbonate (sat.)
  3. extractionextracted with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over anhydrous MgSO4
  6. customThe filtrate was evaporated
  7. customdried in vacuo
  8. customto afford a brown oil, which
  9. customwas purified by Biotage silica chromatography with 20% ethyl acetate in hexane

Sources & evidence

ORD record
ord-73915adffc88495fa14d01aabc711ecf
Source dataset
uspto-grants-2007_08
Patent number
US07259266B2

Reaction notes

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