Triphenylphosphine → HCID 69082913, compound

HRID 2362464Notes

Reaction equation

HRID 2362464 reaction equation
[F:1][C:2]1[CH:7]=[CH:6][C:5]([F:8])=[CH:4][C:3]=1[C@H:9]1[O:13][C:12](=[O:14])[NH:11][C@@H:10]1[C:15]1[CH:16]=[N:17][CH:18]=[C:19]([C:21]#[CH:22])[CH:20]=1.Br[C:24]1[CH:29]=[C:28]([Cl:30])[CH:27]=[C:26]([Cl:31])[CH:25]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C(N(CC)CC)C.[Pd](Cl)Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.[Cu]I>[C:12]([O-:13])(=[O:14])[CH3:24].[NH4+:11].[Cl:30][C:28]1[CH:29]=[C:24]([C:22]#[C:21][C:19]2[CH:20]=[C:15]([C@@H:10]3[C@@H:9]([C:3]4[CH:4]=[C:5]([F:8])[CH:6]=[CH:7][C:2]=4[F:1])[O:13][C:12](=[O:14])[NH:11]3)[CH:16]=[N:17][CH:18]=2)[CH:25]=[C:26]([Cl:31])[CH:27]=1

Participants

8

Reactant 3

HCID 11776TriphenylphosphineHCID 29766Benzene, 1-bromo-3,5-dichloro-HCID 86673452HCID 86673452, compound

Product 2

HCID 517165Ammonium AcetateHCID 69082913HCID 69082913, compoundYield 64.6%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 6102075Dichlorobis(triphenylphosphine)palladiumCatalystHCID 8471TriethylamineSolvent

Procedure

To a slurry of (4R,5R)-5-(2,5-difluorophenyl)-4-(5-ethynylpyridin-3-yl)oxazolidin-2-one (50 mg, 0.167 mmol) in Triethylamine (Volume: 2 mL) was bubbled nitrogen for 20 min at which time 1-bromo-3,5-dichlorobenzene (49 mg, 0.22 mmol) was added with continued nitrogen bubbling for 5 min before adding bis(triphenylphosphine) palladium (II) chloride (8.8 mg, 0.012 mmol), triphenylphosphine (7.9 mg, 0.030 mmol), and copper (I) iodide (9.5 mg, 0.050 mmol) together in 1 portion. After 5 min additional nitrogen bubbling, the vessel was capped and placed in a 70° C. bath. After 18 h, the reaction was cooled, concentrated and diluted with methanol and purified via preparative liquid chromatography (Sunfire C18 OBD 30×100 mm 5 μm, A=95% H2O/5% Acetonitrile, B=95% Acetonitrile/5% H2O, Modifier 10 mM Ammonium Acetate, 0.00 min=20% B, 8.0 min=100% B, 13.0 min=100% B, Flow rate=40 mL/min) providing (4R,5R)-4-(5-((3,5-dichlorophenyl)ethynyl)pyridin-3-yl)-5-(2,5-difluorophenyl)oxazolidin-2-one (24 mg; 32%) as a colorless oil. 1H NMR (500 MHz, CDCl3) δ ppm 8.78 (1H, d, J=1.83 Hz), 8.54 (1H, d, J=1.83 Hz), 7.79-7.97 (1H, m), 7.45 (2H, d, J=1.83 Hz), 7.39 (1H, t, J=1.83 Hz), 7.18-7.32 (2H, m), 7.00-7.18 (1H, m), 5.55 (1H, d, J=5.49 Hz), 5.40 (1H, s), 4.82 (1H, d, J=5.49 Hz), Mass Spectral Anal. Calcd. for [M+H]+ C22H12Cl2F2N2O2: 445.02. found 445.10.

Workup

  1. additionwas added with continued nitrogen bubbling for 5 min
  2. customthe vessel was capped
  3. customplaced in a 70° C.
  4. waitAfter 18 h
  5. temperaturethe reaction was cooled
  6. concentrationconcentrated
  7. additiondiluted with methanol
  8. custompurified via preparative liquid chromatography (Sunfire C18 OBD 30×100 mm 5 μm

Sources & evidence

ORD record
ord-3f61fb06c3e04fffb76c4a8e9a2182f9
Source dataset
uspto-grants-2014_04
Patent number
US08691821B2

Reaction notes

Loading…