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

HRID 250945Notes

Reaction equation

HRID 250945 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-4a23db0a263f4ddea5f985d08143f5d7
Source dataset
uspto-grants-2011_01
Patent number
US07863293B2

Reaction notes

Loading…