Hydrochloric Acid → Methyl 2-(3-tert-butylphenyl)isonicotinate hydrochloride

HRID 1963149Notes

Reaction equation

HRID 1963149 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:12]([C:16]1[CH:17]=[C:18](B2OC(C)(C)C(C)(C)O2)[CH:19]=[CH:20][CH:21]=1)([CH3:15])([CH3:14])[CH3:13].C(=O)([O-])[O-].[K+].[K+].Cl>CO.Cl[Pd]Cl.O.C(Cl)Cl>[ClH:1].[C:12]([C:16]1[CH:21]=[C:20]([C:2]2[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=2)[C:5]([O:7][CH3:8])=[O:6])[CH:19]=[CH:18][CH:17]=1)([CH3:15])([CH3:14])[CH3:13]

Participants

9

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 2736842Methyl 2-chloropyridine-4-carboxylateHCID 222401372-(3-(tert-Butyl)phenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane

Product 1

HCID 66731606Methyl 2-(3-tert-butylphenyl)isonicotinate hydrochlorideYield 70.6%

Reagents, catalysts & solvents 4

HCID 24290Palladium ChlorideCatalystHCID 887MethanolSolvent2×HCID 962WaterSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
100 °C

Procedure

Methyl 2-chloroisonicotinate (1.7 g, 9.91 mmol), 2-(3-tert-butylphenyl)-4,4,5,5-tetramethyl-1,3,2-dioxaborolane (3.393 g, 13.04 mmol), potassium carbonate (2.054 g, 14.86 mmol) and PdCl2 (dppf) (0.215 g, 0.30 mmol) were mixed in methanol (14 mL) in a 20 mL microwave vial. The vial was capped and heated at 100° C. for 10 min in a single node microwave reactor. The reaction mixture was suspended in methanol, the solids removed by filtration and the filtrate evaporated to yield a dark red slurry. DCM and water were added and the phases separated. The water phase (pH 9) was extracted with DCM and the combined organic phase washed with brine, passed through a phase separator and evaporated to a brown solid. The solid was dissolved in MTBE (100 mL) and the solids were filtered off. Hydrogen chloride(4 M in dioxane, 3.50 mL, 13.99 mmol) was added dropwise during stirring and a suspension was formed. The suspension was stirred at room temperature for 3 days. The solid was collected by filtration and washed with MTBE to yield methyl 2-(3-tert-butylphenyl)isonicotinate hydrochloride (2.14 g, 70%) as a slightly brown solid. 1H NMR (600 MHz, cd3od) δ 1.41 (s, 9H), 4.07 (s, 3H), 7.62 (t, 1H), 7.77-7.80 (m, 2H), 8.00-8.02 (m, 1H), 8.37-8.40 (m, 1H), 8.69-8.71 (m, 1H), 8.94-8.97 (m, 1H).

Workup

  1. customThe vial was capped
  2. customthe solids removed by filtration
  3. customthe filtrate evaporated
  4. customto yield a dark red slurry
  5. customthe phases separated
  6. extractionThe water phase (pH 9) was extracted with DCM
  7. washthe combined organic phase washed with brine
  8. customevaporated to a brown solid
  9. dissolutionThe solid was dissolved in MTBE (100 mL)
  10. filtrationthe solids were filtered off
  11. customa suspension was formed
  12. stirringThe suspension was stirred at room temperature for 3 days
  13. filtrationThe solid was collected by filtration
  14. washwashed with MTBE

Sources & evidence

ORD record
ord-9275a89c346c4cad9573f790fafbcfb7
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

Loading…