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

HRID 1398369Notes

Reaction equation

HRID 1398369 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].O1CCOC[CH2:14]1.CB1OB(C)OB(C)O1.C(=O)([O-])[O-].[Cs+].[Cs+]>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].C(Cl)Cl.O>[Cl:12][C:8]1[C:3]([C:4]([O:6][CH3:7])=[O:5])=[C:2]([CH3:14])[N:11]=[CH:10][CH:9]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 312751,4-DioxaneHCID 574072TrimethylboroxineHCID 27282740Methyl 2,4-dichloropyridine-3-carboxylate

Product 1

HCID 84070460Methyl 4-chloro-2-methylpyridine-3-carboxylateYield 58%

Reagents, catalysts & solvents 2

HCID 178418807HCID 178418807, compoundCatalystHCID 962WaterSolvent

Procedure

To a solution of methyl 2,4-dichloronicotinate (10.0 g, 48.5 mmol) in a solvent mixture of 1,4-dioxane (400 mL) and water (40 mL) was added trimethylboroxine (6.79 mL, 48.5 mmol) followed by PdCl2(dppf)-CH2Cl2 adduct (1.982 g, 2.427 mmol) and cesium carbonate (31.6 g, 97 mmol). The reaction mixture was degassed with argon for 5 minutes. The reaction mixture was heated to reflux for 8 h. The reaction mixture was cooled to room temperature and filtered through diatomaceous earth (Celite®). The bed was washed with ethyl acetate and the combined filtrate was concentrated under reduced pressure to afford the crude product which was purified by silica gel column chromatography (gradient of ethyl acetate and petroleum ether) to afford methyl 4-chloro-2-methylnicotinate (5.20 g, 28 mmol, 58% yield) as a yellow liquid. LC/MS (ESI) m/e 185.7 [(M+H)+, calcd for C8H8ClNO2 185.6]; LC/MS retention time (method G): tR=1.90 min.

Workup

  1. customThe reaction mixture was degassed with argon for 5 minutes
  2. temperatureThe reaction mixture was heated
  3. temperatureto reflux for 8 h
  4. filtrationfiltered through diatomaceous earth (Celite®)
  5. washThe bed was washed with ethyl acetate
  6. concentrationthe combined filtrate was concentrated under reduced pressure
  7. customto afford the crude product which
  8. customwas purified by silica gel column chromatography (gradient of ethyl acetate and petroleum ether)

Sources & evidence

ORD record
ord-87f4643478014b4bb6461d3ed13fd82e
Source dataset
uspto-grants-2014_12
Patent number
US08901305B2

Reaction notes

Loading…