Triethylamine → 3-[5-(5-Fluoro-pyridin-3-ylethynyl)-pyridin-2-yl]-5,5-dimethyl-oxazolidin-2-one

HRID 1917542Notes

Reaction equation

HRID 1917542 reaction equation
[CH3:1][C:2]1([CH3:20])[O:6][C:5](=[O:7])[N:4]([C:8]2[CH:13]=[CH:12][C:11]([C:14]#[C:15][Si](C)(C)C)=[CH:10][N:9]=2)[CH2:3]1.[F:21][C:22]1[CH:23]=[N:24][CH:25]=[C:26](I)[CH:27]=1.CCN(CC)CC.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CCCC[N+](CCCC)(CCCC)CCCC.[F-].C([O-])(O)=O.[Na+]>C1COCC1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.Cl[Pd]Cl.[Cu]I>[F:21][C:22]1[CH:27]=[C:26]([C:15]#[C:14][C:11]2[CH:12]=[CH:13][C:8]([N:4]3[CH2:3][C:2]([CH3:20])([CH3:1])[O:6][C:5]3=[O:7])=[N:9][CH:10]=2)[CH:25]=[N:24][CH:23]=1

Participants

10

Reactant 6

HCID 8471TriethylamineHCID 11776Triphenylphosphine2×HCID 516892Sodium BicarbonateHCID 2724141Tetrabutylammonium FluorideHCID 184547783-Fluoro-5-iodopyridineHCID 575167285,5-Dimethyl-3-(5-trimethylsilanylethynyl-pyridin-2-yl)-oxazolidin-2-one

Product 1

HCID 534933613-[5-(5-Fluoro-pyridin-3-ylethynyl)-pyridin-2-yl]-5,5-dimethyl-oxazolidin-2-one

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 8028TetrahydrofuranSolvent2×

Conditions

Temperature
60 °C

Procedure

5,5-Dimethyl-3-(5-trimethylsilanylethynyl-pyridin-2-yl)-oxazolidin-2-one (Example 29, step 1) (100 mg, 0.35 mmol) was dissolved in THF (3 ml). 3-Fluoro-5-iodopyridine (100 mg, 0.45 mmol, 1.3 equiv.), Et3N (145 μl, 1.04 mmol, 3 equiv.), Bis-(triphenylphosphine)-palladium(II)dichloride (10 mg, 14 μmol, 0.05 equiv.), triphenylphosphine (11 mg, 17 μmol, 0.05 equiv.), triphenylphosphine (3 mg, 10 μmol, 0.03 equiv.) and copper(I)iodide (1 mg, 3.5 mmol, 0.01 equiv.) were added under nitrogen and the mixture was heated to 60° C. TBAF 1M in THF (520 μl, 0.52 mmol, 1.5 equiv.) was added dropwise in 20 minutes at 60° C. The reaction mixture was stirred for 3 hours at 60° C. Sat. NaHCO3 solution was added and the mixture was extracted with dichloromethane. The organic extracts were dried with sodium sulfate, filtered and evaporated. The crude product was purified by flash chromatography on silica gel (dichloromethane/methanol gradient 100:0 to 90:10). The desired 3-[5-(5-fluoro-pyridin-3-ylethynyl)-pyridin-2-yl]-5,5-dimethyl-oxazolidin-2-one was obtained as a white solid (55 mg, 51% yield), MS: m/e=312.3 (M+H+).

Workup

  1. extractionthe mixture was extracted with dichloromethane
  2. dry with materialThe organic extracts were dried with sodium sulfate
  3. filtrationfiltered
  4. customevaporated
  5. customThe crude product was purified by flash chromatography on silica gel (dichloromethane/methanol gradient 100:0 to 90:10)

Sources & evidence

ORD record
ord-aaf6c21cfb1246d79589e2c70dc5f35e
Source dataset
uspto-grants-2013_12
Patent number
US08618296B2

Reaction notes

Loading…