Hydrochloric Acid → HCID 66731665, compound

HRID 1963177Notes

Reaction equation

HRID 1963177 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].[Cl:12][C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=1B(O)O.C(=O)([O-])[O-].[K+].[K+].Cl>CO.CC(OC)(C)C.Cl[Pd]Cl>[Cl:12][C:13]1[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=1[C:2]1[CH:3]=[C:4]([CH:9]=[CH:10][N:11]=1)[C:5]([O:7][CH3:8])=[O:6]

Participants

8

Reactant 4

HCID 313Hydrochloric AcidHCID 11430Potassium CarbonateHCID 2736842Methyl 2-chloropyridine-4-carboxylateHCID 177502292-Chloro-4-fluorobenzeneboronic acid

Product 1

HCID 66731665HCID 66731665, compoundYield 43.4%

Reagents, catalysts & solvents 3

HCID 24290Palladium ChlorideCatalystHCID 887MethanolSolventHCID 15413tert-Butyl methyl etherSolvent2×

Conditions

Temperature
100 °C

Procedure

Methyl 2-chloroisonicotinate (3.5 g, 20.40 mmol), 2-chloro-4-fluorophenylboronic acid (3.91 g, 22.44 mmol), potassium carbonate (2.114 g, 15.30 mmol) and PdCl2 (dppf) (0.443 g, 0.61 mmol) were mixed in methanol (30 mL) in two separate 20 mL microwave vials. The vials were capped and heated at 100° C. for 10 min in a single node microwave reactor. Water and DCM were added and the phases were 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 yield a dark-brown solid. The solid was dissolved in MTBE and stirred for 15 minutes, then filtered. The MTBE layer was treated with hydrogen chloride (4 M in dioxane, 5.10 mL, 20.40 mmol) and stirred for 1 h at room temperature. The precipitate was collected by filtration. Methyl 2-(2-chloro-4-fluorophenyl)isonicotinate (2.350 g, 38.1%) was obtained as a light yellow solid. 1H NMR (400 MHz, cdcl3) δ 4.13 (s, 3H), 7.24-7.33 (m, 1H), 7.36 (d, 1H), 7.82-8.03 (m, 1H), 8.34 (s, br., 1H), 8.56 (s, br., 1H), 9.08 (s, br., 1H). MS m/z 266 (M+H)+

Workup

  1. customseparate 20 mL microwave vials
  2. customThe vials were capped
  3. additionWater and DCM were added
  4. customthe phases were separated
  5. extractionThe water phase (pH 9) was extracted with DCM
  6. washthe combined organic phase washed with brine
  7. customevaporated
  8. customto yield a dark-brown solid
  9. filtrationfiltered
  10. stirringstirred for 1 h at room temperature
  11. filtrationThe precipitate was collected by filtration

Sources & evidence

ORD record
ord-8c47e16d8ec04ddd8a22bad2c856f32b
Source dataset
uspto-grants-2013_04
Patent number
US08415378B2

Reaction notes

Loading…