Cesium carbonate → Methyl 4-chloro-2-methylpyridine-3-carboxylate

HRID 1398334Notes

Reaction equation

HRID 1398334 reaction equation
Cl[C:2]1[N:11]=[CH:10][CH:9]=[C:8]([Cl:12])[C:3]=1[C:4]([O:6][CH3:7])=[O:5].[CH3:13]B1OB(C)OB(C)O1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.O.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[Cl:12][C:8]1[C:3]([C:4]([O:6][CH3:7])=[O:5])=[C:2]([CH3:13])[N:11]=[CH:10][CH:9]=1

Participants

7

Reactant 3

HCID 10796Cesium carbonateHCID 574072TrimethylboroxineHCID 27282740Methyl 2,4-dichloropyridine-3-carboxylate

Product 1

HCID 84070460Methyl 4-chloro-2-methylpyridine-3-carboxylateYield 31%

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 962WaterSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
70 °C

Procedure

A mixture of methyl 2,4-dichloronicotinate (2 g, 9.71 mmol), trimethylboroxine (1.462 g, 11.65 mmol), Cs2CO3 (6.33 g, 19.42 mmol) and PdCl2(dppf) (0.710 g, 0.971 mmol) in 1,4-dioxane (30 mL) and water (2 mL) was purged with nitrogen for 5 min and heated at 70° C. for 16 h. The reaction was concentrated under reduced pressure and purified by silica gel column chromatography (EtOAc-hexane mixture) to afford methyl 4-chloro-2-methylnicotinate (550 mg, 2.94 mmol, 31% yield) as a red oil. 1H NMR (300 MHz, CD3OD) δ ppm 8.44 (d, J=5.7 Hz, 1H), 7.43 (d, J=5.7 Hz, 1H), 3.98 (s, 3H), 2.54 (s, 3H).

Workup

  1. customwas purged with nitrogen for 5 min
  2. concentrationThe reaction was concentrated under reduced pressure
  3. custompurified by silica gel column chromatography (EtOAc-hexane mixture)

Sources & evidence

ORD record
ord-70b346e4c7f8438bb5ae98df09063c42
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

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