Potassium Carbonate → HCID 86673452, compound

HRID 2362432Notes

Reaction equation

HRID 2362432 reaction equation
Br[C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:12]([C:13]3[CH:18]=[C:17]([F:19])[CH:16]=[CH:15][C:14]=3[F:20])[O:11][C:10](=[O:21])[NH:9]2)[CH:5]=[N:6][CH:7]=1.[C:22]([Si](C)(C)C)#[CH:23].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[K+].[K+]>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>[F:20][C:14]1[CH:15]=[CH:16][C:17]([F:19])=[CH:18][C:13]=1[C@H:12]1[O:11][C:10](=[O:21])[NH:9][C@@H:8]1[C:4]1[CH:5]=[N:6][CH:7]=[C:2]([C:22]#[CH:23])[CH:3]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 11776TriphenylphosphineHCID 66111TrimethylsilylacetyleneHCID 69083834HCID 69083834, compound

Product 1

HCID 86673452HCID 86673452, compound

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)-4-(5-bromopyridin-3-yl)-5-(2,5-difluorophenyl)oxazolidin-2-one (1.00 g, 2.82 mmol) in triethylamine (30 mL) was bubbled nitrogen for 20 min at which time ethynyltrimethylsilane (0.557 mL, 3.94 mmol) was added with continued nitrogen bubbling for 5 min before adding bis(triphenylphosphine) palladium (II) chloride (0.148 g, 0.211 mmol), triphenylphosphine (0.133 g, 0.507 mmol), and copper (I) iodide (0.161 g, 0.845 mmol) together in 1 portion. After 5 min additional bubbling of nitrogen, the vessel was capped and placed in a 70° C. bath. After 18 h, the vessel was cooled to ambient temperature, concentrated in vacuo dissolved in ethyl acetate, washed with water and brine, dried over MgSO4, filtered and concentrated in vacuo to a black tar which was dissolved in methanol (30 mL). Potassium carbonate (0.428 g, 3.10 mmol) was added and after 30 min, the reaction was concentrated and dissolved in ethyl acetate, washed with water, brine, dried over MgSO4, filtered and concentrated in vacuo to a black tar which was loaded with dichloormethane onto a 40 g silica gel cartridge. Elution with 5 to 75% EtOAc/Hex over 6 column volumes then 75% EtOAc over 2 column volumes. Fractions containing the main peak were concentrated to (4R,5R)-5-(2,5-difluorophenyl)-4-(5-ethynylpyridin-3-yl)oxazolidin-2-one (766 mg; 91%) as a yellow oil which crystallized upon standing. 1H NMR (500 MHz, CDCl3) δ ppm 8.75 (1H, d, J=1.83 Hz), 8.52 (1H, d, J=2.14 Hz), 7.87 (1H, t, J=1.98 Hz), 7.17-7.24 (1H, m), 6.98-7.15 (2H, m), 5.52 (2H, d, J=5.49 Hz), 4.80 (1H, d, J=5.80 Hz), 3.30 (1H, s). Mass Spectral Anal. Calcd. for [M+H]+ C16H10F2N2O2: 301.07. found 301.01.

Workup

  1. additionwas added with continued nitrogen bubbling for 5 min
  2. customAfter 5 min additional bubbling of nitrogen
  3. customthe vessel was capped
  4. customplaced in a 70° C.
  5. concentrationconcentrated in vacuo
  6. dissolutiondissolved in ethyl acetate
  7. washwashed with water and brine
  8. dry with materialdried over MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo to a black tar which
  11. dissolutionwas dissolved in methanol (30 mL)
  12. concentrationthe reaction was concentrated
  13. dissolutiondissolved in ethyl acetate
  14. washwashed with water, brine
  15. dry with materialdried over MgSO4
  16. filtrationfiltered
  17. concentrationconcentrated in vacuo to a black tar which
  18. washElution with 5 to 75% EtOAc/Hex over 6 column volumes
  19. additionFractions containing the main peak
  20. concentrationwere concentrated to (4R,5R)-5-(2,5-difluorophenyl)-4-(5-ethynylpyridin-3-yl)oxazolidin-2-one (766 mg; 91%) as a yellow oil which
  21. customcrystallized

Sources & evidence

ORD record
ord-6413b52eda6b4900a75d1712ab8e1021
Source dataset
uspto-grants-2014_04
Patent number
US08691821B2

Reaction notes

Loading…