Trifluoroacetic acid → (4R,5R)-4-(2-bromo-5-fluoropyridin-4-yl)-5-(4-fluorophenyl)oxazolidin-2-one

HRID 2362371Notes

Reaction equation

HRID 2362371 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([C@@H:8]([NH:18][C:19](=[O:25])[O:20]C(C)(C)C)[C@@H:9]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)O)[C:5]([F:26])=[CH:4][N:3]=1.FC(F)(F)C(O)=O.C(N1C=CN=C1)(N1C=CN=C1)=O>ClCCl>[Br:1][C:2]1[CH:7]=[C:6]([C@@H:8]2[C@@H:9]([C:11]3[CH:12]=[CH:13][C:14]([F:17])=[CH:15][CH:16]=3)[O:20][C:19](=[O:25])[NH:18]2)[C:5]([F:26])=[CH:4][N:3]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 682631,1'-CarbonyldiimidazoleHCID 86673418tert-butyl (1R,2R)-1-(2-bromo-5-fluoropyridin-4-yl)-2-(4-fluorophenyl)-2-hydroxyethylcarbamate

Product 1

HCID 86673419(4R,5R)-4-(2-bromo-5-fluoropyridin-4-yl)-5-(4-fluorophenyl)oxazolidin-2-oneYield 42.9%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a 25 mL round bottom flask was added tert-butyl (1R,2R)-1-(2-bromo-5-fluoropyridin-4-yl)-2-(4-fluorophenyl)-2-hydroxyethylcarbamate (141 mg, 0.328 mmol) in dichloromethane (4 mL). To this solution was added trifluoroacetic acid (0.253 mL, 3.28 mmol) and the reaction was allowed to stir over night at room temperature. The next day the reaction was checked by LC/MS and was complete. The reaction solvent was evaporated in vacuo and the crude oil was diluted with diethylether and washed with saturated sodium bicarbonate. The organic layer was separated, dried over sodium sulfate and the solvent was then evaporated in vacuo and the crude residue was diluted with dry tetrahydrofuran. The solution was cooled to 0° C. and carbonyldiimidazole (53.3 mg, 0.328 mmol) was added and the reaction was allowed to stir overnight. The reaction was complete by LC/MS. The reaction solvent was then evaporated in vacuo and the crude solid was purified by silica gel chromatography 15% EtOAc/85% Hexanes to 50% EtOAc/50% Hexanes affording (4R,5R)-4-(2-bromo-5-fluoropyridin-4-yl)-5-(4-fluorophenyl)oxazolidin-2-one (20 mg, 0.056 mmol, 42.9% yield) and its regioisomer as an inseparable mixture. LC/Mass spec. (Analytical HPLC method 2): RT=1.79 min. Mass=354.89 (MH)+.

Workup

  1. customThe reaction solvent was evaporated in vacuo
  2. additionthe crude oil was diluted with diethylether
  3. washwashed with saturated sodium bicarbonate
  4. customThe organic layer was separated
  5. dry with materialdried over sodium sulfate
  6. customthe solvent was then evaporated in vacuo
  7. additionthe crude residue was diluted with dry tetrahydrofuran
  8. temperatureThe solution was cooled to 0° C.
  9. stirringto stir overnight
  10. customThe reaction solvent was then evaporated in vacuo
  11. customthe crude solid was purified by silica gel chromatography 15% EtOAc/85% Hexanes to 50% EtOAc/50% Hexanes

Sources & evidence

ORD record
ord-169bf24d6cbe463c9994255772cd0061
Source dataset
uspto-grants-2014_04
Patent number
US08691821B2

Reaction notes

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