Sodium Carbonate → HCID 21883708, compound

HRID 722327Notes

Reaction equation

HRID 722327 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4](I)[C:5]2[O:10][CH:9]([C:11]([F:14])([F:13])[F:12])[C:8]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:7][C:6]=2[CH:20]=1.[CH3:22][O:23][C:24]1[CH:25]=[C:26](B(O)O)[CH:27]=[CH:28][CH:29]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>C(O)CC.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.O>[Cl:1][C:2]1[CH:3]=[C:4]([C:28]2[CH:27]=[CH:26][CH:25]=[C:24]([O:23][CH3:22])[CH:29]=2)[C:5]2[O:10][CH:9]([C:11]([F:14])([F:13])[F:12])[C:8]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[CH:7][C:6]=2[CH:20]=1

Participants

8

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 2734370(3-Methoxyphenyl)boronic acidHCID 21883552ethyl 6-chloro-8-iodo-2-(trifluoromethyl)-2H-chromene-3-carboxylate

Product 1

HCID 21883708HCID 21883708, compound

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 962WaterSolventHCID 10311-PropanolSolvent

Procedure

In a 100 mL round bottomed flask under nitrogen, ethyl 6-chloro-8-iodo-2-(trifluoromethyl)-2H-1-benzopyran-3-carboxylate (Example 73, Step 2) (1.00 g, 2.31 mmol) and 3-methoxyphenylboronic acid (0.369 g, 2.43 mmol) were dissolved in 1-propanol (50 mL). The mixture was stirred at room temperature for 0.5 hours, allowing for the solids to dissolve. The resulting solution was treated with palladium (II) acetate (0.016 g, 0.0693 mmol), triphenylphosphine (0.055 g, 0.208 mmol), sodium carbonate (0.294 g, 2.77 mmol), and deionized water (10 mL). The reaction mixture was heated to reflux for 3 hours. After cooling to room temperature the mixture was extracted with ethyl acetate (1×150 mL, 2×25 mL). The combined organic phases were washed with saturated aqueous NaHCO3 (50 mL) and brine (2×50 mL), dried over MgSO4, filtered, and concentrated in vacuo to yield a yellow oil. The crude material was purified by flash chromatography in 0.5% ethyl acetate in hexane yielding a white solid. The solid was recrystallized from hexane yielding the desired ester as a white solid (0.60 g, 63%): mp 93.7–95.1° C. 1H NMR (CDCl3/300 MHz) 7.69 (s, 1H), 7.35–7.32 (m, 2H), 7.22 (d, 1H, J=2.6 Hz), 7.05–7.03 (m, 2H), 6.96–6.93 (m, 1H), 5.72 (q, 1H, J=6.7 Hz), 4.34–4.31 (m, 2H), 1.35 (t, 3H, J=7.1 Hz). FABLRMS m/z 413 (M+H). ESHRMS m/z 413.0765 (M+H, Calc'd. 413.076747). Anal. Calc'd. for C20H16ClF3O4: C, 58.19; H, 3.91; Cl, 8.59. Found: C, 58.33; H, 4.10; Cl, 8.61.

Workup

  1. dissolutionto dissolve
  2. temperatureThe reaction mixture was heated
  3. temperatureto reflux for 3 hours
  4. temperatureAfter cooling to room temperature the mixture
  5. extractionwas extracted with ethyl acetate (1×150 mL, 2×25 mL)
  6. washThe combined organic phases were washed with saturated aqueous NaHCO3 (50 mL) and brine (2×50 mL)
  7. dry with materialdried over MgSO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo
  10. customto yield a yellow oil
  11. customThe crude material was purified by flash chromatography in 0.5% ethyl acetate in hexane yielding a white solid
  12. customThe solid was recrystallized from hexane yielding the desired ester as a white solid (0.60 g, 63%)

Sources & evidence

ORD record
ord-1662808b0f204b34944fb65c856314e2
Source dataset
uspto-grants-2006_11
Patent number
US07138411B2

Reaction notes

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