Trifluoroacetic acid → (4R,5R)-4-(5-bromo-2-fluoropyridin-3-yl)-5-(3-fluorophenyl)oxazolidin-2-one

HRID 2362363Notes

Reaction equation

HRID 2362363 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][CH:15]=[C:14]([F:18])[CH:13]=2)O)[C:5]([F:8])=[N:6][CH:7]=1.FC(F)(F)[C:29]([OH:31])=[O:30].C(N1C=CN=C1)([N:36]1C=CN=C1)=O>ClCCl.N.CO.O1CCCC1>[Br:1][C:2]1[CH:3]=[C:4]([C@@H:9]2[C@@H:10]([C:12]3[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=3)[O:26][C:20](=[O:21])[NH:19]2)[C:5]([F:8])=[N:6][CH:7]=1.[Br:1][C:2]1[CH:3]=[C:4]([C@H:9]2[O:31][C:29](=[O:30])[NH:36][C@@H:10]2[C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([F:18])[CH:13]=2)[C:5]([F:8])=[N:6][CH:7]=1

Participants

9

Reactant 3

HCID 6422Trifluoroacetic acidHCID 682631,1'-CarbonyldiimidazoleHCID 70958019tert-butyl (1R,2R)-1-(5-bromo-2-fluoropyridin-3-yl)-2-(3-fluorophenyl)-2-hydroxyethylcarbamate

Product 2

HCID 69083956(4R,5R)-4-(5-bromo-2-fluoropyridin-3-yl)-5-(3-fluorophenyl)oxazolidin-2-oneYield 13.55%HCID 70945669(4R,5R)-5-(5-bromo-2-fluoropyridin-3-yl)-4-(3-fluorophenyl)oxazolidin-2-oneYield 9.2%

Reagents, catalysts & solvents 4

HCID 222AmmoniaSolventHCID 887MethanolSolventHCID 6344DichloromethaneSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a 25 mL round bottom flask was added tert-butyl (1R,2R)-1-(5-bromo-2-fluoropyridin-3-yl)-2-(3-fluorophenyl)-2-hydroxyethylcarbamate (223 mg, 0.520 mmol) in dichloromethane (4 mL). To this solution was added trifluoroacetic acid (1.014 mL, 13.16 mmol) and the reaction was allowed to stir over night at room temperature. The reaction solvent was then evaporated in vacuo. The crude reaction mixture was then dissolved in 5 mL of 2N ammonia in methanol and stirred for 5 min. The solvent was then evaporated in vacuo and the crude residue was diluted with dry tetrahydrofuran (4 mL) and carbonyldiimidazole (168 mg, 1.039 mmol) was added and the reaction was stirred at room temperature for 1 hr. The reaction solvent was then evaporated in vacuo and the crude solid was purified by silica gel chromatography 10% EtOAc/90% Hexanes to 30% EtOAc/70% Hexanes affording (4R,5R)-4-(5-bromo-2-fluoropyridin-3-yl)-5-(3-fluorophenyl)oxazolidin-2-one (25 mg, 0.070 mmol, 13.55% yield) and (4R,5R)-5-(5-bromo-2-fluoropyridin-3-yl)-4-(3-fluorophenyl)oxazolidin-2-one (17 mg, 0.048 mmol, 9.2% yield) as an inseparable mixture. 1H-NMR (CDCl3, 400 MHz) δ 8.33 (d, J=2.3, 1H), 7.47-7.41 (m, 1H), 7.19-7.11 (m, 3H), 5.64 (s, 1H), 5.36 (d, J=5.0, 1H), 5.00 (d, J=5.0, 1H), LC/Mass spec. (Analytical HPLC method 2): RT=2.09 min. Mass=355.09 (MH)+.

Workup

  1. customThe reaction solvent was then evaporated in vacuo
  2. customThe crude reaction mixture
  3. stirringstirred for 5 min
  4. customThe solvent was then evaporated in vacuo
  5. additionwas added
  6. stirringthe reaction was stirred at room temperature for 1 hr
  7. customThe reaction solvent was then evaporated in vacuo
  8. customthe crude solid was purified by silica gel chromatography 10% EtOAc/90% Hexanes to 30% EtOAc/70% Hexanes

Sources & evidence

ORD record
ord-17df66d06f844a21b5530af7b0cb80dc
Source dataset
uspto-grants-2014_04
Patent number
US08691821B2

Reaction notes

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