Triethylamine → HCID 68983260, compound

HRID 1821718Notes

Reaction equation

HRID 1821718 reaction equation
[C:1]1([C:7]2[C:8]([CH2:16][C:17]([NH2:19])=O)=[C:9]3[N:14]([CH:15]=2)[CH:13]=[CH:12][CH:11]=[CH:10]3)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.C(N(CC)CC)C.[C:27](Cl)(=[O:30])[CH2:28][CH3:29]>ClC(Cl)C.C(Cl)Cl.O>[C:17]([CH2:16][C:8]1[C:7]([C:1]2[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=2)=[C:15]([C:27](=[O:30])[CH2:28][CH3:29])[N:14]2[C:9]=1[CH:10]=[CH:11][CH:12]=[CH:13]2)#[N:19]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 62324Propionyl chlorideHCID 68982764HCID 68982764, compound

Product 1

HCID 68983260HCID 68983260, compound

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 63651,1-DichloroethaneSolvent

Conditions

Temperature
70 °C

Procedure

2-(2-Phenylindolizin-1-yl)acetamide (1.0 g, 40 mmol) was dissolved in dichloroethane (35 mL) containing triethylamine (0.65 mL). To the stirred solution was added propionyl chloride (0.70 mL). The reaction mixture was heated in an oil bath (70° C.) over the weekend. After cooling, the reaction mixture was diluted with methylene chloride and water. The phases were separated and the aqueous phase was extracted with methylene chloride 3 times. Evaporation of the combined organic layers gave a residue which was purified by column chromatography on silica gel eluting with 1.0-1.2% methanol in methylene chloride to give 115 mg of 1-cyanomethyl-3-propionyl-2-phenylindolizine. The cyanomethyl keto indolizine was reduced to the title compound with lithium aluminum hydride (150 mg) in ethyl ether under reflux in a nitrogen atmosphere overnight. After cooling the reaction mixture was quenched with Rochelle salt and stirred to give a solution. The phases were separated and the aqueous phase was extracted with ether and then made basic with 2.5 N NaOH. The crude product was extracted into methylene chloride and the solvent removed under reduced pressure to give a residue which was purified on silica gel eluting with 9% methanol in methylene chloride to give 70 mg of the free base of the title compound. The free base was dissolved in ethanol to which an ethanolic solution of 70 mg of fumaric acid was added. The solution was evaporated and the residue was recrystallized from methyl ethyl ketone to give the fumaric acid salt of the title compound, mp: 169-172° C.; MS [M+H]+ 279 m/z; Microanalysis was consistent for C19H22N2+C4H4O4+0.7 H2O

Workup

  1. temperatureAfter cooling
  2. customThe phases were separated
  3. extractionthe aqueous phase was extracted with methylene chloride 3 times
  4. customEvaporation of the combined organic layers
  5. customgave a residue which
  6. customwas purified by column chromatography on silica gel eluting with 1.0-1.2% methanol in methylene chloride

Sources & evidence

ORD record
ord-22c5f2b47bc848f18dcc2d5536418052
Source dataset
uspto-grants-2009_10
Patent number
US07608626B2

Reaction notes

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