Hydrochloric Acid → HCID 66732376, compound

HRID 1963204Notes

Reaction equation

HRID 1963204 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6].C(=O)([O-])[O-].[K+].[K+].[Cl:18][C:19]1[C:24]([F:25])=[CH:23][C:22](B2OC(C)(C)C(C)(C)O2)=[CH:21][C:20]=1[F:35].Cl>CO.Cl[Pd]Cl>[ClH:1].[Cl:18][C:19]1[C:24]([F:25])=[CH:23][C:22]([C:2]2[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=2)[C:5]([O:7][CH3:8])=[O:6])=[CH:21][C:20]=1[F:35]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 2736842Methyl 2-chloropyridine-4-carboxylateHCID 667350322-(4-Chloro-3,5-difluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Product 1

HCID 66732376HCID 66732376, compoundYield 42%

Reagents, catalysts & solvents 2

HCID 24290Palladium ChlorideCatalystHCID 887MethanolSolvent

Conditions

Temperature
100 °C

Procedure

Methyl 2-chloroisonicotinate (3.01 g, 17.53 mmol), PdCl2 (dppf) (0.317 g, 0.44 mmol) and potassium carbonate (1.322 mL, 21.91 mmol) were distributed equally over 3 microwave reaction vials. 2-(4-Chloro-3,5-difluorophenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (4.01 g, 14.61 mmol) was dissolved in methanol (45 mL) to give a colorless solution. The solution was split into 3 equal portions and added to the vials. The vials were capped and heated in a single node microwave reactor at 100° C. for 10 min each. The content of the vials was combined and the solvent evaporated. The residue was dissolved in DCM and washed with water. The organic phase was filtered through a phase separator and evaporated. The residue was dissolved in MTBE and solids were filtered off. Hydrogen chloride (4 M in dioxane, 3.65 mL, 14.61 mmol) was added and the precipitate collected to yield methyl 2-(4-chloro-3,5-difluorophenyl)isonicotinate hydrochloride (1.72 g, 42%) as a solid. 1H NMR (400 MHz, cdcl3) δ 4.06 (s, 3H), 7.86 (d, 2H), 8.09 (d, 1H), 8.39 (s, 1H), 8.96 (d, 1H). MS m/z 284 (M+H)+

Workup

  1. customto give a colorless solution
  2. customThe solution was split into 3 equal portions
  3. additionadded to the vials
  4. customThe vials were capped
  5. customthe solvent evaporated
  6. dissolutionThe residue was dissolved in DCM
  7. washwashed with water
  8. filtrationThe organic phase was filtered through a phase separator
  9. customevaporated
  10. dissolutionThe residue was dissolved in MTBE
  11. filtrationsolids were filtered off
  12. customthe precipitate collected

Sources & evidence

ORD record
ord-39230bac1d7c478b931aaaa2bf92eb94
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

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