2-Methyltetrahydrofuran → Tert-butyl 4-[4-iodo-1-(2-pyrrolidin-1-ylethyl)imidazol-2-yl]piperidine-1-carboxylate

HRID 2088919

Reaction equation

HRID 2088919 reaction equation
[I:1][C:2]1[N:3]=[C:4]([CH:15]2[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]2)[N:5]([CH2:8][CH2:9][N:10]2[CH2:14][CH2:13][CH2:12][CH2:11]2)[C:6]=1I.CC1CCCO1.C([Mg]Cl)(C)C.O1CCCC1>O.C(O)(=O)C>[I:1][C:2]1[N:3]=[C:4]([CH:15]2[CH2:20][CH2:19][N:18]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH2:17][CH2:16]2)[N:5]([CH2:8][CH2:9][N:10]2[CH2:14][CH2:13][CH2:12][CH2:11]2)[CH:6]=1

Participants

7

Reactant 4

HCID 73012-MethyltetrahydrofuranHCID 8028TetrahydrofuranHCID 67112102Tert-butyl 4-[4,5-diiodo-1-(2-pyrrolidin-1-ylethyl)imidazol-2-yl]piperidine-1-carboxylateHCID 178418918HCID 178418918, compound

Product 1

HCID 67112018Tert-butyl 4-[4-iodo-1-(2-pyrrolidin-1-ylethyl)imidazol-2-yl]piperidine-1-carboxylateYield 94.1%

Reagents, catalysts & solvents 2

HCID 176Acetic AcidSolventHCID 962WaterSolvent

Procedure

Combine tert-butyl 4-[4,5-diiodo-1-(2-pyrrolidin-1-ylethyl)imidazol-2-yl]piperidine-1-carboxylate (39 g, 64.97 mmol) and 2-methyltetrahydrofuran (273 mL), then cool to −15° C. Add 2 M isopropylmagnesium chloride in tetrahydrofuran (32.48 mL, 1.0 eq) dropwise over 45 minutes, maintaining the temperature below −10° C. Stir for an additional 30 min. Add acetic acid (7.45 mL) dropwise, then water (120 mL). Wash the aqueous phase with methyl tert-butyl ether (2×50 mL). Wash the organics with aqueous saturated sodium chloride. Dry the organics over anhydrous magnesium sulfate and concentrate in vacuo. Crystallize the resulting oil from hexanes/methyl tert-butyl ether to give tert-butyl 4-[4-iodo-1-(2-pyrrolidin-1-ylethyl)imidazol-2-yl]piperidine-1-carboxylate as a white solid (29 g, 94%). MS (ES) m/z=475 [M]+.

Workup

  1. temperaturemaintaining the temperature below −10° C
  2. washWash the aqueous phase with methyl tert-butyl ether (2×50 mL)
  3. washWash the organics with aqueous saturated sodium chloride
  4. dry with materialDry the organics over anhydrous magnesium sulfate
  5. concentrationconcentrate in vacuo
  6. customCrystallize the resulting oil from hexanes/methyl tert-butyl ether

Sources & evidence

ORD record
ord-02ec8b593e744bcf8a78e573d26ca337
Source dataset
uspto-grants-2013_05
Patent number
US08436002B2

Linked notes

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