Methanol → (4R,5R)-4-(2-fluoro-5-((2-fluoropyridin-4-yl)ethynyl)pyridin-3-yl)-5-(3-fluorophenyl)oxazolidin-2-one

HRID 2362451Notes

Reaction equation

HRID 2362451 reaction equation
[C:1]([C:3]1[CH:4]=[C:5]([C@@H:10]2[C@@H:14]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=3)[O:13][C:12](=[O:22])[NH:11]2)[C:6]([F:9])=[N:7][CH:8]=1)#[CH:2].Br[C:24]1[CH:29]=[CH:28][N:27]=[C:26]([F:30])[CH:25]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CO>C(N(CC)CC)C.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[F:9][C:6]1[C:5]([C@@H:10]2[C@@H:14]([C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([F:21])[CH:16]=3)[O:13][C:12](=[O:22])[NH:11]2)=[CH:4][C:3]([C:1]#[C:2][C:24]2[CH:29]=[CH:28][N:27]=[C:26]([F:30])[CH:25]=2)=[CH:8][N:7]=1

Participants

8

Reactant 4

HCID 887MethanolHCID 11776TriphenylphosphineHCID 27628514-Bromo-2-fluoropyridineHCID 86673416(4R,5R)-4-(5-ethynyl-2-fluoropyridin-3-yl)-5-(3-fluorophenyl)oxazolidin-2-one

Product 1

HCID 69083238(4R,5R)-4-(2-fluoro-5-((2-fluoropyridin-4-yl)ethynyl)pyridin-3-yl)-5-(3-fluorophenyl)oxazolidin-2-oneYield 31.4%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolvent

Conditions

Temperature
90 °C

Procedure

To a 15 ml sealable vial was added (4R,5R)-4-(5-ethynyl-2-fluoropyridin-3-yl)-5-(3-fluorophenyl)oxazolidin-2-one (20 mg, 0.067 mmol) in triethylamine (2 mL). To this suspension was added 4-bromo-2-fluoropyridine (15.24 mg, 0.087 mmol), triphenylphosphine (5.24 mg, 0.020 mmol) and copper(I) iodide (0.254 mg, 1.332 μmol). The solution was degassed with nitrogen for 20 min, then bis(triphenylphosphine)palladium(II) chloride (0.935 mg, 1.332 μmol) was quickly added and the vial was sealed, heated to 90° C., and allowed to stir overnight. The next day the suspension had turned homogeneous and the reaction was cooled to room temperature and the solvent was evaporated in vacuo. The crude residue was purified by silica gel chromotagraphy eluting first with 100% CH2Cl2 then 1% MeOH/99% CH2Cl2 affording (4R,5R)-4-(2-fluoro-5-((2-fluoropyridin-4-yl)ethynyl)pyridin-3-yl)-5-(3-fluorophenyl)oxazolidin-2-one (9.1 mg, 0.021 mmol, 31.4% yield) as a light yellow solid. 1H-NMR (CDCl3, 400 MHz) δ 8.63 (s, 1H), 8.51 (d, J=4.0, 1H), 8.45 (s, 1H), 8.14 (dd, J=8.0, 4.0, 1H), 7.69-7.64 (m, 1H), 7.60-7.54 (m, 1H), 7.50-7.43 (m, 1H), 7.21-7.13 (m, 2H), 6.05 (brs, 1H), 5.39 (d, J=4.0, 1H), 5.04 (d, J=4.0, 1H), LC/Mass spec. (Analytical HPLC method 2): RT=2.01 min. Mass=396.20 (MH)+.

Workup

  1. customThe solution was degassed with nitrogen for 20 min
  2. customthe vial was sealed
  3. temperaturethe reaction was cooled to room temperature
  4. customthe solvent was evaporated in vacuo
  5. customThe crude residue was purified by silica gel chromotagraphy
  6. washeluting first with 100% CH2Cl2

Sources & evidence

ORD record
ord-af9b2ab6867e4d9982b0216a0db92d23
Source dataset
uspto-grants-2014_04
Patent number
US08691821B2

Reaction notes

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