Potassium Phosphate, Tribasic → (E)-Methyl 2-(4-fluorostyryl)isonicotinate

HRID 1963257Notes

Reaction equation

HRID 1963257 reaction equation
Cl[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6].[F:12][C:13]1[CH:23]=[CH:22][C:16](/[CH:17]=[CH:18]/B(O)O)=[CH:15][CH:14]=1.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>Cl[Pd]Cl>[F:12][C:13]1[CH:23]=[CH:22][C:16](/[CH:17]=[CH:18]/[C:2]2[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=2)[C:5]([O:7][CH3:8])=[O:6])=[CH:15][CH:14]=1

Participants

5

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 2736842Methyl 2-chloropyridine-4-carboxylateHCID 5706776trans-2-(4-Fluorophenyl)vinylboronic acid

Product 1

HCID 66732050(E)-Methyl 2-(4-fluorostyryl)isonicotinateYield 47.1%

Reagents, catalysts & solvents 1

HCID 24290Palladium ChlorideCatalyst

Conditions

Temperature
100 °C

Procedure

Methyl 2-chloroisonicotinate (5.5 g, 32.05 mmol), (E)-4-fluorostyrylboronic acid (7.98 g, 48.08 mmol), potassium phosphate (3.93 mL, 48.08 mmol) and PdCl2 (dppf) (0.464 g, 0.64 mmol) were split into 5 equal portions and each portion was placed in a microwave reaction vessel. The vessels were evacuated and backfilled with nitrogen. Methanol (15 mL) was added to each vessel, the vessels were sealed and heated in a single node microwave reactor at 100° C. for 10 min each. The contents of the vessels was pooled and water and DCM were added, the phases separated and the aqueous layer was extracted with DCM. The combined organic layers were filtered through a phase separator and evaporated. The residue was purified by automated flash chromatography on a Biotage® KP-SIL 340 g column. A gradient from 6:1 to 4:1 of EtOAc in heptane over 15 CV was used as mobile phase. (E)-Methyl 2-(4-fluorostyryl)isonicotinate (3.88 g, 47%) was isolated. 1H NMR (400 MHz, cdcl3) δ 3.98 (s, 3H), 7.04-7.18 (m, 3H), 7.52-7.62 (m, 2H), 7.63-7.71 (m, 2H), 7.93 (s, 1H), 8.74 (d, 1H). MS m/z 258 (M+H)+

Workup

  1. customeach portion was placed in a microwave reaction vessel
  2. customThe vessels were evacuated
  3. additionMethanol (15 mL) was added to each vessel
  4. customthe vessels were sealed
  5. additionwater and DCM were added
  6. customthe phases separated
  7. extractionthe aqueous layer was extracted with DCM
  8. filtrationThe combined organic layers were filtered through a phase separator
  9. customevaporated
  10. customThe residue was purified by automated flash chromatography on a Biotage® KP-SIL 340 g column

Sources & evidence

ORD record
ord-70c9b288aee14cb696c1a5193439166f
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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