Sodium Sulfite → HCID 178452530, compound

HRID 625578Notes

Reaction equation

HRID 625578 reaction equation
[I:1][C:2]1[N:3]=[C:4]([C@@H:8]2[CH2:13][C@@H:12]3[C@@H:10]([CH2:11]3)[N:9]2[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[NH:5][C:6]=1I.S([O-])([O-])=O.[Na+].[Na+]>CCO.O>[I:1][C:2]1[N:3]=[C:4]([C@@H:8]2[CH2:13][C@@H:12]3[C@@H:10]([CH2:11]3)[N:9]2[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15])[NH:5][CH:6]=1.[NH:3]1[CH:2]=[CH:6][N:5]=[C:4]1[C@@H:8]1[CH2:13][C@@H:12]2[C@@H:10]([CH2:11]2)[N:9]1[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15]

Participants

6

Reactant 2

HCID 24437Sodium SulfiteHCID 58498721HCID 58498721, compound

Product 2

HCID 58498829HCID 58498829, compoundYield 13%HCID 178452530HCID 178452530, compoundYield 62%

Reagents, catalysts & solvents 2

HCID 702EthanolSolventHCID 962WaterSolvent

Conditions

Temperature
90 °C

Procedure

A 250 mL pressure flask equipped with a stir bar was charge with a solution of (1R,3S,5R)-tert-butyl 3-(4,5-diiodo-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (8.3 g, 17 mmol) in EtOH (83 mL) and water (83 mL). Then, sodium sulfite (20.88 g, 166 mmol) was added and the mixture was heated at 90° C. for 16 h. The reaction mixture was extracted with EtOAc and the combined organic layers were dried over Na2SO4 and evaporated under vacuum. The residue was purified by flash column chromatography (BIOTAGE®), eluting with a gradient of 0 to 15% EtOAc/DCM to afford (1R,3S,5R)-tert-butyl 3-(4-iodo-1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (3.84 g, 10.2 mmol, 62% yield) as yellow solid along with the fully reduced product (1R,3S,5R)-tert-butyl 3-(1H-imidazol-2-yl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (550 mg, 2.21 mmol, 13% yield). LC-MS retention time 0.932 min; m/z 376.22 (MH+). LC data was recorded on a Shimadzu LC-10AS liquid chromatograph equipped with a Waters Sunfire 5u C18 4.6×30 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 2 min, a hold time of 1 min, and an analysis time of 3 min where Solvent A was 10% MeOH/90% H2O/0.1% TFA and Solvent B was 10% H2O/90% MeOH/0.1% TFA. MS data was determined using a MICROMASS® Platform for LC in electrospray mode. 1H NMR (500 MHz, MeOD) δ ppm 7.12 (br s, 1H), 4.59 (br s, 1H), 3.44-3.64 (br s, 1H), 2.40-2.52 (m, 1H), 2.17-2.30 (m, 1H), 1.65-1.73 (m, 1H), 1.27 (br s, 9H), 0.84 (dt, J=8.5, 5.7 Hz, 1H), 0.58 (br s, 1H).

Workup

  1. customA 250 mL pressure flask equipped with a stir bar
  2. extractionThe reaction mixture was extracted with EtOAc
  3. dry with materialthe combined organic layers were dried over Na2SO4
  4. customevaporated under vacuum
  5. customThe residue was purified by flash column chromatography (BIOTAGE®)
  6. washeluting with a gradient of 0 to 15% EtOAc/DCM

Sources & evidence

ORD record
ord-91619ecc39ef496cb090d84388f31a4b
Source dataset
uspto-grants-2016_04
Patent number
US09303007B2

Reaction notes

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