1,1'-Carbonyldiimidazole → HCID 86673410, compound

HRID 2362339Notes

Reaction equation

HRID 2362339 reaction equation
[Br:1][C:2]1[N: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][CH:3]=1.C(N1C=CN=C1)(N1C=CN=C1)=O>FC(F)(F)C(O)=O>[Br:1][C:2]1[N: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][CH:3]=1

Participants

4

Reactant 2

HCID 682631,1'-CarbonyldiimidazoleHCID 86673407HCID 86673407, compound

Product 1

HCID 86673410HCID 86673410, compound

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

(±)-tert-Butyl (1R,2R)-1-(6-bromopyridin-2-yl)-2-hydroxy-2-phenylethylcarbamate (1.1 g, 1.40 mmol) was dissolved in trifluoroacetic acid (25% in dichloromethane, 25 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 (25 mL), cooled to 0° C., and treated with carbonyldiimidazole (580 mg, 3.58 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 treated with an additional portion of carbonyldiimidazole (90 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 nearly pure product. The material was further purified by trituration of the solid with diethyl ether. 1H-NMR (CDCl3, 500 MHz) δ 7.65 (dd, J=7.6, 7.6, 1H), 7.52 (d, J=7.6, 1H), 7.37-7.50 (m, 6H), 6.83 (bs, 1H), 5.63 (d, J=5.5, 1H), 4.92 (d, J=5.5, 1H). 13C-NMR (CDCl3, 126 MHz) δ 159.9, 159.2, 142.6, 139.7, 138.2, 129.13, 129.08, 128.2, 125.8, 119.6, 83.6, 64.4. Mass spec.: 319.1 (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. additionThe reaction was treated with an additional portion of carbonyldiimidazole (90 mg)
  12. stirringstirred at room temperature for 2 h
  13. customThe reaction was quenched by addition of 2M ammonia in methanol
  14. concentrationconcentrated
  15. customThe resulting residue was purified by column chromatography (25%-->50% EtOAc/Hex)
  16. customto give nearly pure product
  17. customThe material was further purified by trituration of the solid with diethyl ether

Sources & evidence

ORD record
ord-e95006d21c3b4757928b8fb40e61e1b8
Source dataset
uspto-grants-2014_04
Patent number
US08691821B2

Reaction notes

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