Hydrogen Peroxide → Methyl 3-(cyanomethyl)-5,6,7,8-tetrahydroindolizine-2-carboxylate

HRID 1024089Notes

Reaction equation

HRID 1024089 reaction equation
[CH:1]1[C:2]([C:10]([O:12][CH3:13])=[O:11])=[CH:3][N:4]2[C:9]=1[CH2:8][CH2:7][CH2:6][CH2:5]2.I[CH2:15][C:16]#[N:17].OO>O.O.O.O.O.O.O.S([O-])([O-])(=O)=O.[Fe+2].CS(C)=O>[C:16]([CH2:15][C:3]1[N:4]2[C:9]([CH2:8][CH2:7][CH2:6][CH2:5]2)=[CH:1][C:2]=1[C:10]([O:12][CH3:13])=[O:11])#[N:17]

Participants

6

Reactant 3

HCID 784Hydrogen Peroxide2×HCID 69356IodoacetonitrileHCID 13115072Methyl 5,6,7,8-Tetrahydroindolizine-2-carboxylate

Product 1

HCID 58044124Methyl 3-(cyanomethyl)-5,6,7,8-tetrahydroindolizine-2-carboxylateYield 78.4%

Reagents, catalysts & solvents 2

HCID 62662Ferrous sulfate heptahydrateCatalyst3×HCID 679Dimethyl SulfoxideSolvent

Procedure

A 500-mL three-neck round-bottomed flask equipped with an addition funnel, thermometer and charged with 120a (6.70 g, 37.4 mmol), iodoacetonitrile (12.5 g, 74.9 mmol), iron (II) sulfate heptahydrate (5.20 g, 18.7 mmol) and dimethyl sulfoxide (250 mL). Hydrogen peroxide (35%, 18.2 g, 187 mmol) was added dropwise to the mixture over the period of 1 h through a syringe pump at room temperature using a water bath. Iron (II) sulfate heptahydrate (2 to 3 equivalent) was added to the reaction mixture in portions to keep the temperature between 25° C. to 35° C., until the color of the reaction mixture was deep red. When TLCs showed the reaction was not complete, more hydrogen peroxide (2-3 equivalent) and more iron (II) sulfate heptahydrate (1-2 equivalents) were added in the same manner until the reaction was complete. After that time, the reaction mixture was partitioned between saturated sodium bicarbonate solution (200 mL) and ethyl acetate (400 mL). The organic layer was separated, and the aqueous layer was extracted with ethyl acetate (2×100 mL). The combined organic layers were washed with saturated sodium thiosulfate solution (50 mL), dried over sodium sulfate and concentrated under reduced pressure. The residue was purified by column chromatography to afford a 78% yield (6.40 g) of 120b as a yellow oil: 1H NMR (500 MHz, CDCl3) δ 6.23 (s, 1H), 4.23 (s, 2H), 3.94 (t, 2H, J=6.5 Hz), 3.81 (s, 3H), 2.74 (t, 2H, J=6.5 Hz), 2.00 (m, 2H), 1.83 (m, 2H); (APCI+) m/z 219.3 (M+H)

Workup

  1. customA 500-mL three-neck round-bottomed flask equipped with an addition funnel
  2. custombetween 25° C. to 35° C.
  3. customAfter that time, the reaction mixture was partitioned between saturated sodium bicarbonate solution (200 mL) and ethyl acetate (400 mL)
  4. customThe organic layer was separated
  5. extractionthe aqueous layer was extracted with ethyl acetate (2×100 mL)
  6. washThe combined organic layers were washed with saturated sodium thiosulfate solution (50 mL)
  7. dry with materialdried over sodium sulfate
  8. concentrationconcentrated under reduced pressure
  9. customThe residue was purified by column chromatography

Sources & evidence

ORD record
ord-32d5c2ef5b97444bbfc0d77b814ad990
Source dataset
uspto-grants-2014_05
Patent number
US08722676B2

Reaction notes

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