Trifluoroacetic acid → HCID 69086172, compound

HRID 2362368Notes

Reaction equation

HRID 2362368 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C@@H:9]([NH:19][C:20](=[O:26])[O:21]C(C)(C)C)[C@@H:10]([C:12]2[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=2)O)[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:12]3[CH:13]=[CH:14][C:15]([F:18])=[CH:16][CH:17]=3)[O:26][C:20](=[O:21])[NH:19]2)[C:5]([F:8])=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 682631,1'-CarbonyldiimidazoleHCID 70958312HCID 70958312, compound

Product 1

HCID 69086172HCID 69086172, compoundYield 15%

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-(4-fluorophenyl)-2-hydroxyethylcarbamate (1450 mg, 3.38 mmol) in dichloromethane (12 mL). To this solution was added trifluoroacetic acid (2.60 mL, 33.8 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 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 (282 mg, 1.74 mmol) was added and the reaction was allowed to stir overnight. The reaction solvent was then evaporated in vacuo and the crude residue was diluted with 2N ammonia in methanol and stirred for 15 min. The 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 the desired product and its regioisomer as an inseparable mixture. The inseparable mixture was further purified by reverse phase chromatography using a sunfire col 30×100 45%-55% MeOH/H2O 0.1% TFA over a 20 minute run time affording (4R,5R)-4-(5-bromo-2-fluoropyridin-3-yl)-5-(4-fluorophenyl)oxazolidin-2-one (180 mg, 0.507 mmol, 10.99% yield). 1H-NMR (CDCl3, 400 MHz) δ 8.33 (s, 1H), 8.10 (d, J=8.0), 7.42-7.38 (m, 2H), 7.19-7.15 (m, 2H), 5.81 (brs, 1H), 5.36 (d, J=4.0, 1H), 5.01 (d, J=4.0, 1H), LC/Mass spec. (Analytical HPLC method 2): RT=2.17 min. Mass=356.96 (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. additionthe crude residue was diluted with 2N ammonia in methanol
  12. stirringstirred for 15 min
  13. customThe solvent was then evaporated in vacuo
  14. customthe crude solid was purified by silica gel chromatography 15% EtOAc/85% Hexanes to 50% EtOAc/50% Hexanes affording the desired product and its regioisomer as an inseparable mixture
  15. customThe inseparable mixture was further purified by reverse phase chromatography
  16. customover a 20 minute

Sources & evidence

ORD record
ord-ef0df49f6d0e4295bc47f50c911be985
Source dataset
uspto-grants-2014_04
Patent number
US08691821B2

Reaction notes

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