1,1'-Carbonyldiimidazole → (4R,5R)-4-(5-bromopyridin-3-yl)-5-(3-methoxyphenyl)oxazolidin-2-one

HRID 2362348Notes

Reaction equation

HRID 2362348 reaction equation
[Br:1][C:2]1[CH:3]=[C:4]([C@@H:8]([NH:19][C:20](=[O:26])[O:21]C(C)(C)C)[C@H:9](O)[C:10]2[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH3:17])[CH:11]=2)[CH:5]=[N:6][CH:7]=1.C(N1C=CN=C1)(N1C=CN=C1)=O>FC(F)(F)C(O)=O>[Br:1][C:2]1[CH:3]=[C:4]([C@@H:8]2[C@@H:9]([C:10]3[CH:15]=[CH:14][CH:13]=[C:12]([O:16][CH3:17])[CH:11]=3)[O:26][C:20](=[O:21])[NH:19]2)[CH:5]=[N:6][CH:7]=1

Participants

4

Reactant 2

HCID 682631,1'-CarbonyldiimidazoleHCID 70958320tert-butyl (1R,2R)-1-(5-bromopyridin-3-yl)-2-hydroxy-2-(3-methoxyphenyl)ethylcarbamate

Product 1

HCID 69086194(4R,5R)-4-(5-bromopyridin-3-yl)-5-(3-methoxyphenyl)oxazolidin-2-one

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

Optically-enriched tert-butyl (1R,2R)-1-(5-bromopyridin-3-yl)-2-hydroxy-2-(3-methoxyphenyl)ethylcarbamate (3.76 g, 4.44 mmol) was dissolved in trifluoroacetic acid (25% in dichloromethane, 40 mL) and stirred at room temperature for 1 h. 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 (40 mL), cooled to 0° C., and treated with carbonyldiimidazole (1.46 g, 9.00 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 (500 mg) and stirred at room temperature for 1 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 660 mg (21%). 1H-NMR (CDCl3, 500 MHz) δ 8.69 (d, J=2.1, 1H), 8.39 (d, J=2.1, 1H), 7.92 (dd, J=2.1, 1.8, 1H), 7.34 (dd, J=7.9, 7.9, 1H), 6.95 (dd, J=8.6, 1.8, 1H), 6.77-6.91 (m, 3H), 5.22 (d, J=7.6, 1H), 4.82 (d, J=7.6, 1H), 3.82 (s, 3H). 13C-NMR (CDCl3, 126 MHz) δ 160.3, 158.9, 151.7, 146.4, 137.8, 136.7, 136.0, 130.5, 121.6, 118.1, 115.2, 111.4, 85.6, 62.2, 55.5. Mass spec.: 349.12 (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 (500 mg)
  13. stirringstirred at room temperature for 1 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 660 mg (21%)

Sources & evidence

ORD record
ord-f62bb207ec844d95ba5fd4e5be7eadba
Source dataset
uspto-grants-2014_04
Patent number
US08691821B2

Reaction notes

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