2-Chloro-3-(2,2,2-trifluoroethoxy)pyridine → HCID 20675886, compound

HRID 1592383Notes

Reaction equation

HRID 1592383 reaction equation
Cl[C:2]1[C:7]([O:8][CH2:9][C:10]([F:13])([F:12])[F:11])=[CH:6][CH:5]=[CH:4][N:3]=1.[CH3:14][Mg+].[Br-]>CCOCC.[Ni](Cl)Cl.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[CH3:14][C:2]1[C:7]([O:8][CH2:9][C:10]([F:13])([F:12])[F:11])=[CH:6][CH:5]=[CH:4][N:3]=1

Participants

5

Reactant 2

HCID 120567282-Chloro-3-(2,2,2-trifluoroethoxy)pyridineHCID 178418689HCID 178418689, compound

Product 1

HCID 20675886HCID 20675886, compound

Reagents, catalysts & solvents 2

HCID 2724937Dichloro(1,1'-(1,3-propanediyl)bis(1,1-diphenylphosphine-kappaP))nickelCatalystHCID 3283Diethyl EtherSolvent

Procedure

2-Chloro-3-(2,2,2-trifluoro-ethoxy)-pyridine (1.21 g, 5.73 mmol) (Hoglen, D. K. PCT Int. Appl. (2000), WO 2000005212) and 1,3-bis(diphenylphosphino)propane nickel (II) chloride (217 mg, 0.40 mmol) were taken up in Et2O (40 mL) at room temperature. MeMgBr (3.0M in Et2O, 2.25 ml, 5.73 mmol) was added dropwise via syringe over 3 minutes to give a tan slurry. The mixture was refluxed for 16 h, cooled to room temperature, quenched with water (60 mL) and extracted with CH2Cl2 (8×50 mL). The combined organic extracts were dried (Na2SO4), filtered, and concentrated in vacuo to afford 2-methyl-3-(2,2,2-trifluoro-ethoxy)-pyridine as an orange oil. Purification via column chromatography on silica gel (CH2Cl2) afforded 2-methyl-3-(2,2,2-trifluoro-ethoxy)-pyridine as a yellow solid (0.46 g, 42%). 1H NMR (CDCl3) δ 2.52 (s, 3H), 4.36 (q, 2H, J=7.5 Hz), 7.06-7.14 (m, 2H), 8.19 (d, 1H, J=3.0 Hz). 19F NMR (CDCl3) δ 2.03 (s).

Workup

  1. customto give a tan slurry
  2. temperatureThe mixture was refluxed for 16 h
  3. customquenched with water (60 mL)
  4. extractionextracted with CH2Cl2 (8×50 mL)
  5. dry with materialThe combined organic extracts were dried (Na2SO4)
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-68804595527b4a549b28c1222ca3dda4
Source dataset
uspto-grants-2007_11
Patent number
US07291631B2

Reaction notes

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