1,1'-Carbonyldiimidazole → HCID 86673444, compound

HRID 2362422Notes

Reaction equation

HRID 2362422 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)[C:5]([F:25])=[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:19][C:18](=[O:24])[NH:17]2)[C:5]([F:25])=[CH:4][CH:3]=1

Participants

4

Reactant 2

HCID 682631,1'-CarbonyldiimidazoleHCID 86673443HCID 86673443, compound

Product 1

HCID 86673444HCID 86673444, compound

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Conditions

Temperature
0 °C

Procedure

Optically-enriched tert-butyl (1R,2R)-1-(6-bromo-3-fluoropyridin-2-yl)-2-hydroxy-2-phenylethylcarbamate (208 mg, 0.506 mmol) was dissolved in trifluoroacetic acid (25% in dichloromethane, 10 mL). After 2 h at room temperature, the reaction was concentrated. The resulting residue was loaded onto a strong cation exchange cartridge which was flushed with several volumes of methanol and discarded. The product was eluted with 2M ammonia in methanol and concentrated. The resulting residue was suspended in tetrahydrofuran (2 mL), cooled to 0° C., and treated with carbonyldiimidazole (123 mg, 0.759 mmol). After 5 min, the ice bath was removed and stirring continued overnight. 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 96 mg (28%) as a white foam solid. Mass spec.: 337.0 (MH)+.

Workup

  1. concentrationthe reaction was concentrated
  2. customwas flushed with several volumes of methanol
  3. washThe product was eluted with 2M ammonia in methanol
  4. concentrationconcentrated
  5. waitAfter 5 min
  6. customthe ice bath was removed
  7. customThe reaction was quenched by addition of 2M ammonia in methanol
  8. concentrationconcentrated
  9. customThe resulting residue was purified by column chromatography (25%→50% EtOAc/Hex)
  10. customto give 96 mg (28%) as a white foam solid

Sources & evidence

ORD record
ord-f4967c1e50204d828e662c795f73c048
Source dataset
uspto-grants-2014_04
Patent number
US08691821B2

Reaction notes

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