Trifluoroacetic acid → HCID 69085210, compound

HRID 2362374Notes

Reaction equation

HRID 2362374 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C@@H:9]([NH:22][C:23](=[O:29])[O:24]C(C)(C)C)[C@H:10](O)[C:11]2[CH:16]=[CH:15][C:14]([C:17]([F:20])([F:19])[F:18])=[CH:13][CH:12]=2)[C:5]([F:8])=[N:6][CH:7]=1.FC(F)(F)C(O)=O.C(N1C=CN=C1)(N1C=CN=C1)=O>ClCCl>[Br:1][C:2]1[CH:3]=[C:4]([C@@H:9]2[C@@H:10]([C:11]3[CH:12]=[CH:13][C:14]([C:17]([F:18])([F:19])[F:20])=[CH:15][CH:16]=3)[O:29][C:23](=[O:24])[NH:22]2)[C:5]([F:8])=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 682631,1'-CarbonyldiimidazoleHCID 86673420HCID 86673420, compound

Product 1

HCID 69085210HCID 69085210, compoundYield 39.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a 25 mL round bottom flask was added tert-butyl (1R,2R)-1-(5-bromo-2-fluoropyridin-3-yl)-2-hydroxy-2-(4-(trifluoromethyl)phenyl)ethylcarbamate (250 mg, 0.53 mmol) in dichloromethane (8 mL). To this solution was added trifluoroacetic acid (1.021 mL, 13.25 mmol) and the reaction was allowed to stir over night at room temperature. The reaction solvent was evaporated in vacuo and the crude oil was diluted with ethylacetate 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 (86 mg, 0.530 mmol) was added and the reaction was allowed to stir overnight. 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-(5-bromo-2-fluoropyridin-3-yl)-5-(4-(trifluoromethyl)phenyl)oxazolidin-2-one (84 mg, 0.207 mmol, 39.1% yield) and its regioisomer as an inseparable mixture. LC/Mass spec. (Analytical HPLC method 2): RT=2.44 min. Mass=406.91 (MH)+.

Workup

  1. customThe reaction solvent was evaporated in vacuo
  2. additionthe crude oil was diluted with ethylacetate
  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-c2fd7a40d3d9412cbb55f738746f1717
Source dataset
uspto-grants-2014_04
Patent number
US08691821B2

Reaction notes

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