Triethylamine → 3-(3-Fluoro-5-(phenylethynyl)pyridin-2-yl)-5,5-dimethyloxazolidin-2-one

HRID 1966561Notes

Reaction equation

HRID 1966561 reaction equation
[F:1][C:2]1[C:3]([N:9]2[CH2:13][C:12]([CH3:15])([CH3:14])[O:11][C:10]2=[O:16])=[N:4][CH:5]=[C:6](I)[CH:7]=1.[C:17]1([C:23]#[CH:24])[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.C(N(CC)CC)C>CN(C=O)C.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.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:1][C:2]1[C:3]([N:9]2[CH2:13][C:12]([CH3:15])([CH3:14])[O:11][C:10]2=[O:16])=[N:4][CH:5]=[C:6]([C:24]#[C:23][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH:7]=1

Participants

8

Reactant 3

HCID 8471TriethylamineHCID 10821PhenylacetyleneHCID 575167133-(3-Fluoro-5-iodopyridin-2-yl)-5,5-dimethyloxazolidin-2-one

Product 1

HCID 534931043-(3-Fluoro-5-(phenylethynyl)pyridin-2-yl)-5,5-dimethyloxazolidin-2-oneYield 86.6%

Reagents, catalysts & solvents 4

HCID 11776TriphenylphosphineCatalystHCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
70 °C

Procedure

Bis-(triphenylphosphine)-palladium(II)dichloride (12.5 mg, 17.9 μmol, 0.05 equiv.) was dissolved in 1 ml DMF. (120 mg, 357 μmol) 3-(3-Fluoro-5-iodopyridin-2-yl)-5,5-dimethyloxazolidin-2-one (Example 1, step 2) and phenylacetylene (72.9 mg, 78.4 μl, 714 μmol, 2 equiv.) were added at room temperature. Triethylamine (108 mg, 149 μl, 1.07 mmol, 3 equiv.), triphenylphosphine (2.81 mg, 10.7 μmol, 0.03 equiv.) and copper(I) iodide (2.04 mg, 10.7 μmol, 0.03 equiv.) were added and the mixture was stirred for 3 hours at 70° C. The reaction mixture was cooled and extracted with saturated NaHCO3 solution and two times with a small volume of dichloromethane. The crude product was purified by flash chromatography by directly loading the dichloromethane layers onto a silica gel column and eluting with an ethyl acetate:heptane gradient 0:100 to 40:60. The desired 3-(3-fluoro-5-(phenylethynyl)pyridin-2-yl)-5,5-dimethyloxazolidin-2-one (96 mg, 309 μmol, 86.6% yield) was obtained as a yellow solid, MS: m/e=311.2 (M+H+).

Workup

  1. temperatureThe reaction mixture was cooled
  2. extractionextracted with saturated NaHCO3 solution and two times with a small volume of dichloromethane
  3. customThe crude product was purified by flash chromatography
  4. washeluting with an ethyl acetate

Sources & evidence

ORD record
ord-15404d3401ea4aa1a64e23e4f596d2f9
Source dataset
uspto-grants-2013_04
Patent number
US08420661B2

Reaction notes

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