Dimethylformamide → Methyl 3-formyl-5,6,7,8-tetrahydroindolizine-2-carboxylate

HRID 1411752Notes

Reaction equation

HRID 1411752 reaction equation
ClC(Cl)C.CN([CH:8]=[O:9])C.P(Cl)(Cl)(Cl)=O.[CH:15]1[C:16]([C:24]([O:26][CH3:27])=[O:25])=[CH:17][N:18]2[C:23]=1[CH2:22][CH2:21][CH2:20][CH2:19]2>C(#N)C>[CH:8]([C:17]1[N:18]2[C:23]([CH2:22][CH2:21][CH2:20][CH2:19]2)=[CH:15][C:16]=1[C:24]([O:26][CH3:27])=[O:25])=[O:9]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 63651,1-DichloroethaneHCID 24813Phosphorus oxychlorideHCID 13115072Methyl 5,6,7,8-Tetrahydroindolizine-2-carboxylate

Product 1

HCID 86683769Methyl 3-formyl-5,6,7,8-tetrahydroindolizine-2-carboxylateYield 60.6%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

A 100-mL round-bottomed flask equipped with a magnetic stirrer was purged with nitrogen and charged with anhydrous dichloroethane (20 mL) and anhydrous DMF (0.70 mL, 9.0 mmol). To the mixture at 0° C. was added phosphorus oxychloride (0.70 mL, 7.3 mmol) over a period of 2 min, while maintaining the reaction temperature between 0° C. and 10° C. The cooling bath was removed and the reaction was stirred at room temperature for 1 hour. A solution of 193c (1.0 g, 5.6 mmol) in acetonitrile (10 mL) was added and the reaction mixture was stirred at room temperature for 3 hours. After this time, it was concentrated under reduced pressure. The oily residue was taken up with saturated aqueous NaHCO3 (20 mL) and extracted with ethyl acetate (3×50 mL). The combined organic layer was washed with water (50 mL), dried over Na2SO4, and evaporated under reduced pressure. The residue was purified by silica-gel column chromatography eluting with 1:5 ethyl acetate/petroleum ether to afford 193d as a white solid (703 mg, 58%). MS-ESI: (M+H)+ 208.3. 1H NMR (500 MHz, DMSO-d6) δ 10.14 (s, 1H), 6.40 (s, 1H), 4.27 (t, J=6.0 Hz, 2H), 3.78 (s, 3H), 2.78 (t, J=6.0 Hz, 2H), 1.94-1.85 (m, 2H), 1.78-1.69 (m, 2H).

Workup

  1. customA 100-mL round-bottomed flask equipped with a magnetic stirrer
  2. customwas purged with nitrogen
  3. temperaturewhile maintaining the reaction temperature between 0° C. and 10° C
  4. customThe cooling bath was removed
  5. stirringthe reaction mixture was stirred at room temperature for 3 hours
  6. concentrationAfter this time, it was concentrated under reduced pressure
  7. extractionextracted with ethyl acetate (3×50 mL)
  8. washThe combined organic layer was washed with water (50 mL)
  9. dry with materialdried over Na2SO4
  10. customevaporated under reduced pressure
  11. customThe residue was purified by silica-gel column chromatography
  12. washeluting with 1:5 ethyl acetate/petroleum ether

Sources & evidence

ORD record
ord-6c9ca65eb4e14815899f60da7eb7318d
Source dataset
uspto-grants-2014_12
Patent number
US08921353B2

Reaction notes

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