1,1'-Carbonyldiimidazole → (4R,5R)-4-(2-Bromopyridin-4-yl)-5-phenyloxazolidin-2-one

HRID 2362343Notes

Reaction equation

HRID 2362343 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([C@@H:8]([NH:17][C:18](=[O:24])[O:19]C(C)(C)C)[C@H:9](O)[C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:5]=[CH:4][N:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=O>FC(F)(F)C(O)=O>[Br:1][C:2]1[CH:7]=[C:6]([C@@H:8]2[C@@H:9]([C:10]3[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=3)[O:24][C:18](=[O:19])[NH:17]2)[CH:5]=[CH:4][N:3]=1

Participants

4

Reactant 2

HCID 682631,1'-CarbonyldiimidazoleHCID 86673412tert-butyl (1R,2R)-1-(2-bromopyridin-4-yl)-2-hydroxy-2-phenylethylcarbamate

Product 1

HCID 86673413(4R,5R)-4-(2-Bromopyridin-4-yl)-5-phenyloxazolidin-2-one

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

Optically-enriched tert-butyl (1R,2R)-1-(2-bromopyridin-4-yl)-2-hydroxy-2-phenylethylcarbamate (1.85 g, 2.35 mmol) was dissolved in trifluoroacetic acid (25% in dichloromethane, 40 mL) and stirred at room temperature for 1 h. LC/MS shows clean conversion to product. The reaction was concentrated, dissolved in methanol, and loaded onto a strong cation exchange cartridge. The cartridge was flushed with several volumes of methanol which were discarded. The product was eluted with 2M ammonia in methanol and concentrated. The resulting residue was suspended in tetrahydrofuran (50 mL), cooled to 0° C., and treated with carbonyldiimidazole (0.763 g, 4.70 mmol) in a single portion. The resulting suspension was stirred at 0° C. for 5 min. The ice bath was removed and stirring continued for 1 h. The reaction was re-cooled to 0° C., and treated with an additional portion of carbonyldiimidazole (160 mg) and stirred at room temperature for 2 h. The reaction was quenched by addition of 2M ammonia in methanol and concentrated. The resulting residue was purified by column chromatography (25%-->50% EtOAc/Hex) to give the optically-enriched product. The minor enantiomer was removed by SFC Prep HPLC (Chiralpak AS-H, 25% MeOH in CO2) to give 452 mg (30%). 1H-NMR (CDCl3, 500 MHz) δ 8.42 (d, J=5.2, 1H), 7.40-7.56 (m, 4H), 7.33 (m, 2H), 7.19 (dd, J=5.2, 1.2, 1H), 6.95 (bs, 1H), 5.21 (d, J=7.3, 1H), 4.81 (d, J=7.3, 1H). 13C-NMR (CDCl3, 126 MHz) δ 158.9, 151.1, 150.6, 143.3, 136.4, 129.9, 129.4, 126.2, 125.6, 120.3, 85.3, 63.4. Mass spec.: 319.04 (MH)+.

Workup

  1. concentrationThe reaction was concentrated
  2. dissolutiondissolved in methanol
  3. customThe cartridge was flushed with several volumes of methanol which
  4. washThe product was eluted with 2M ammonia in methanol
  5. concentrationconcentrated
  6. temperaturecooled to 0° C.
  7. stirringThe resulting suspension was stirred at 0° C. for 5 min
  8. customThe ice bath was removed
  9. stirringstirring
  10. waitcontinued for 1 h
  11. temperatureThe reaction was re-cooled to 0° C.
  12. additiontreated with an additional portion of carbonyldiimidazole (160 mg)
  13. stirringstirred at room temperature for 2 h
  14. customThe reaction was quenched by addition of 2M ammonia in methanol
  15. concentrationconcentrated
  16. customThe resulting residue was purified by column chromatography (25%-->50% EtOAc/Hex)
  17. customto give the optically-enriched product
  18. customThe minor enantiomer was removed by SFC Prep HPLC (Chiralpak AS-H, 25% MeOH in CO2)
  19. customto give 452 mg (30%)

Sources & evidence

ORD record
ord-3b7d3245618147afb79ae613f7487b65
Source dataset
uspto-grants-2014_04
Patent number
US08691821B2

Reaction notes

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