4-Fluorostyrene → HCID 22050124, compound

HRID 1831982Notes

Reaction equation

HRID 1831982 reaction equation
FC(F)(F)S(O[C:7]1[CH:12]=[CH:11][N:10]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=2)[C:9](=[O:21])[C:8]=1[Br:22])(=O)=O.[F:25][C:26]1[CH:33]=[CH:32][C:29]([CH:30]=[CH2:31])=[CH:28][CH:27]=1.C(N(C(C)C)CC)(C)C>CN(C=O)C.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Br:22][C:8]1[C:9](=[O:21])[N:10]([CH2:13][C:14]2[CH:19]=[CH:18][CH:17]=[C:16]([F:20])[CH:15]=2)[CH:11]=[CH:12][C:7]=1/[CH:31]=[CH:30]/[C:29]1[CH:32]=[CH:33][C:26]([F:25])=[CH:27][CH:28]=1

Participants

6

Reactant 3

HCID 678834-FluorostyreneHCID 81531DiisopropylethylamineHCID 58710194HCID 58710194, compound

Product 1

HCID 22050124HCID 22050124, compoundYield 6.5%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
65 °C

Procedure

A mixture of 3-bromo-1-(3-fluorobenzyl)-2-oxo-1,2-dihydropyridin-4-yl trifluoromethanesulfonate (1.0 g, 0.0023 mol), and 4-fluorostyrene (0.33 mL, 0.0028 mol) in degassed DMF (100 ml) containing diisopropyl ethyl amine (0.37 g, 0.0029 mol) was treated with PdCl2(PPh3)2 (0.32 g, 0.46 mmol) and heated at 65° C. under argon atmosphere for 16 h. DMF was distilled in vacuo, and the residue was purified by flash chromatography (EtOAc/hexane 1:4 v/v) to afford a yellow substance which was further purified by by reverse-phase HPLC using 10-90% acetonitrile/water gradient (30 min), at flow rate of 100 mL/min. The appropriate fractions were combined, concentrated to a small volume (20 mL), added EtOAc (25 mL) and washed successively with satd. sod. bicarbonate, water, and dried (Na2SO4). EtOAc was removed under reduced pressure and residue was dried in vacuo to afford the title compound (0.06 g, 6%) as yellow powder: 1H NMR (CD3OD/400 MHz) δ 7.68 (m, 3H), 7.39 (m, 3H), 7.2-7.0 (m, 5H), 6.82 (d, 1H, J=7.2 Hz), and 5.22 (s, 2H); 19F NMR (CD3OD/400 MHz) δ−113.9 (m) and −115 (m); ES-HRMS m/z 402.0305 (M+HC20H15NOF2Br, requires 402.0300).

Workup

  1. distillationDMF was distilled in vacuo
  2. customthe residue was purified by flash chromatography (EtOAc/hexane 1:4 v/v)
  3. customto afford a yellow substance which
  4. customwas further purified by by reverse-phase
  5. custom10-90% acetonitrile/water gradient (30 min)
  6. concentrationconcentrated to a small volume (20 mL)
  7. additionadded EtOAc (25 mL)
  8. washwashed successively with satd
  9. dry with materialbicarbonate, water, and dried (Na2SO4)
  10. customEtOAc was removed under reduced pressure and residue
  11. customwas dried in vacuo

Sources & evidence

ORD record
ord-39b560a4d51146ca8747d4bc3d22c94f
Source dataset
uspto-grants-2006_06
Patent number
US07067540B2

Reaction notes

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