Sodium Sulfite → (S)-tert-butyl 2-(5-iodo-1H-imidazol-2-yl)pyrrolidine-1-carboxylate

HRID 625557Notes

Reaction equation

HRID 625557 reaction equation
S([O-])([O-])=O.[Na+].[Na+].[I:7][C:8]1[N:9]=[C:10]([C@@H:14]2[CH2:18][CH2:17][CH2:16][N:15]2[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[NH:11][C:12]=1I>C(O)C.O.C(OCC)(=O)C>[I:7][C:8]1[NH:9][C:10]([C@@H:14]2[CH2:18][CH2:17][CH2:16][N:15]2[C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])=[N:11][CH:12]=1

Participants

6

Reactant 2

HCID 24437Sodium SulfiteHCID 59449990(S)-tert-butyl 2-(4,5-diiodo-1H-imidazol-2-yl)-pyrrolidine-1-carboxylate

Product 1

HCID 58498756(S)-tert-butyl 2-(5-iodo-1H-imidazol-2-yl)pyrrolidine-1-carboxylateYield 73.1%

Reagents, catalysts & solvents 3

HCID 702EthanolSolventHCID 962WaterSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
90 °C

Procedure

Sodium sulfite (10.31 g, 82 mmol) was added to a solution of (S)-tert-butyl 2-(4,5-diiodo-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (4.0 g, 8.2 mmol) in ethanol (75 mL) and water (75 mL). The suspension was heated with an oil bath at 100° C. for 4 hours and at 90° C. for 16 h. The reaction was diluted with ethyl acetate and water. The layers were separated and the aqueous layer was extracted several times with ethyl acetate. The combined organic phases were dried (brine, Na2SO4), filtered and concentrated in vacuo. The residue was purified by a flash chromatography (sample was dry loaded on silica gel and eluted with, 0 to 40% ethyl acetate/CH2Cl2) to afford (S)-tert-butyl 2-(5-iodo-1H-imidazol-2-yl)pyrrolidine-1-carboxylate (2.17 g, 73.1%) as a white solid. LC-MS retention time 0.930 min; calcd. for C12H181 N3O2 363.04. found m/z 364.06 [M+H]+. LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters Sunfire 5u C18 4.6×50 mm column using a SPD-10AV UV-Vis detector at a detector wave length of 220 nM. The elution conditions employed a flow rate of 4 mL/min, a gradient of 100% Solvent A/0% Solvent B to 0% Solvent A/100% Solvent B, a gradient time of 3 min, a hold time of 1 min and an analysis time of 4 min where Solvent A was 10% acetonitrile/90% water/0.1% TFA and Solvent B was 90% acetonitrile/10% water/0.1% TFA. 1H NMR (500 MHz, MeOD) δ ppm 7.52-7.64 (m, 1H), 4.95-5.10 (m, 1H), 3.57-3.70 (m, 1H), 3.47-3.57 (m, 1H), 2.37-2.55 (m, 1H), 1.94-2.10 (m, 3H), 1.46 (s, 4H), 1.27 (s, 5H).

Workup

  1. customThe layers were separated
  2. extractionthe aqueous layer was extracted several times with ethyl acetate
  3. dry with materialThe combined organic phases were dried (brine, Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe residue was purified by a flash chromatography (sample was dry loaded on silica gel and eluted with, 0 to 40% ethyl acetate/CH2Cl2)

Sources & evidence

ORD record
ord-6c4156a7117a47db89730e8bc822bc50
Source dataset
uspto-grants-2016_04
Patent number
US09303007B2

Reaction notes

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