Ammonium Chloride → (2S,4S)-tert-butyl 2-(5-iodo-1H-imidazol-2-yl)-4-methylpyrrolidine-1-carboxylate

HRID 1625522Notes

Reaction equation

HRID 1625522 reaction equation
[Li+].[Cl-].[I:3][C:4]1[N:5]=[C:6]([C@@H:10]2[CH2:14][C@H:13]([CH3:15])[CH2:12][N:11]2[C:16]([O:18][C:19]([CH3:22])([CH3:21])[CH3:20])=[O:17])[NH:7][C:8]=1I.C[Mg]Cl.C([Mg]Cl)(C)C.[NH4+].[Cl-]>C1COCC1.O>[I:3][C:4]1[N:5]=[C:6]([C@@H:10]2[CH2:14][C@H:13]([CH3:15])[CH2:12][N:11]2[C:16]([O:18][C:19]([CH3:20])([CH3:22])[CH3:21])=[O:17])[NH:7][CH:8]=1

Participants

8

Reactant 5

HCID 25517Ammonium ChlorideHCID 433294Lithium ChlorideHCID 53261950(2S,4S)-tert-butyl 2-(4,5-diiodo-1H-imidazol-2-yl)-4-methylpyrrolidine-1-carboxylateHCID 178418332HCID 178418332, compoundHCID 178418918HCID 178418918, compound

Product 1

HCID 53261949(2S,4S)-tert-butyl 2-(5-iodo-1H-imidazol-2-yl)-4-methylpyrrolidine-1-carboxylateYield 84.7%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent3×

Procedure

A solution of LiCl in THF (3.9 mL of a 0.5 M solution, 1.99 mmol) is added to tert-butyl (2S,4S)-2-(4,5-diiodo-1H-imidazol-2-yl)-4-methyl-pyrrolidine-1-carboxylate (1 g, 1.99 mmol). After stirring for 5 minutes at rt the reaction mixture is cooled down to −20° C. and a solution of methyl magnesium chloride in THF (946.7 μL of 2.1 M, 1.99 mmol) is added dropwise. After stirring for 20 minutes at −20° C., a solution of isopropyl magnesium chloride in THF (3.2 mL of 1.24 M, 3.97 mmol) is added dropwise. The reaction mixture is slowly warmed up to rt and stirred for 2 hours. The reaction mixture is cooled down to 0° C. and a saturated aqueous NH4Cl solution is slowly added followed by water. This mixture is then extracted with EtOAc (3×20 mL), and the combined organic layers are washed with brine, dried over Na2SO4, filtered and concentrated to dryness. The residue is purified by flash column chromatography on silica gel (0 to 25% EtOAC/Hexane) to afford tert-butyl (2S,4S)-2-(4-iodo-1H-imidazol-2-yl)-4-methyl-pyrrolidine-1-carboxylate (636 mg, 83%) as a white solid.

Workup

  1. temperatureis cooled down to −20° C.
  2. stirringAfter stirring for 20 minutes at −20° C.
  3. temperatureThe reaction mixture is slowly warmed up to rt
  4. stirringstirred for 2 hours
  5. temperatureThe reaction mixture is cooled down to 0° C.
  6. extractionThis mixture is then extracted with EtOAc (3×20 mL)
  7. washthe combined organic layers are washed with brine
  8. dry with materialdried over Na2SO4
  9. filtrationfiltered
  10. concentrationconcentrated to dryness
  11. customThe residue is purified by flash column chromatography on silica gel (0 to 25% EtOAC/Hexane)

Sources & evidence

ORD record
ord-87bbd130ae2d4180b58f495fb4d61112
Source dataset
uspto-grants-2014_07
Patent number
US08779156B2

Reaction notes

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