Carbon Dioxide → N,N-diethyl-1-(phenylmethyl)-3-pyrrolidinemethanamine

HRID 1198606Notes

Reaction equation

HRID 1198606 reaction equation
O=[C:2]1[N:6]([CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:5][CH:4]([C:14](O)=O)[CH2:3]1.C[N:18]1[CH2:23][CH2:22]O[CH2:20][CH2:19]1.ClC(OCC)=O.C(NCC)C.C(=O)=O.[H-].[Al+3].[Li+].[H-].[H-].[H-]>ClCCl.O1CCCC1>[CH2:19]([N:18]([CH2:23][CH3:22])[CH2:14][CH:4]1[CH2:3][CH2:2][N:6]([CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:5]1)[CH3:20]

Participants

9

Reactant 6

HCID 280Carbon DioxideHCID 79724-MethylmorpholineHCID 8021Diethylamine2×HCID 10928Ethyl chloroformateHCID 990241-Benzyl-5-oxo-pyrrolidine-3-carboxylic acidHCID 21226445Aluminium lithium hydride

Product 1

HCID 14075472N,N-diethyl-1-(phenylmethyl)-3-pyrrolidinemethanamineYield 69.8%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent3×HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-25 °C

Procedure

To a solution of 32.9 g (0.15 mole) 5-oxo-1-(phenylmethyl)-3-pyrrolidinecarboxylic acid [J. Org. Chem., 26, 1519 (1961)] and 300 mL of dichloromethane was added 15.2 g (0.15 mole) of N-methylmorpholine. After 15 minutes the solution was cooled to -25° C. and 16.3 g (0.15 mole) of ethyl chloroformate was added. After an additional ten minutes, a solution of 13.5 g (0.18 mole) of diethylamine and 18 mL dichloromethane was added to the reaction. Carbon dioxide was evolved and after 1.5 h another 10 g (0.13 mole) of diethylamine in 10 mL of dichlormethane was added. The reaction was stirred four hours, washed with 1N sodium hydroxide, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was added to a suspension of 17.4 g (0.46 mole) of lithium aluminum hydride and 210 mL anhydrous tetrahydrofuran. The reaction was refluxed overnight then cooled to room temperature. The cooled solution was quenched by the successive addition of 17.4 mL water, 17.4 mL 15% sodium hydroxide, and 52.2 mL water. The resulting precipitate was filtered and washed with ethyl alcohol. The filtrate was concentrated under reduced pressure, taken up in dichloromethane and dried over magnesium sulfate. The solvent was removed under vacuum giving 25.8 g (69%) of N,N-diethyl-1-(phenylmethyl)-3-pyrrolidinemethanamine as a yellow oil. This material was used in the next step without purification.

Workup

  1. waitAfter an additional ten minutes
  2. washwashed with 1N sodium hydroxide
  3. dry with materialdried over magnesium sulfate
  4. concentrationconcentrated under reduced pressure
  5. temperatureThe reaction was refluxed overnight
  6. temperaturethen cooled to room temperature
  7. customThe cooled solution was quenched by the successive addition of 17.4 mL water, 17.4 mL 15% sodium hydroxide, and 52.2 mL water
  8. filtrationThe resulting precipitate was filtered
  9. washwashed with ethyl alcohol
  10. concentrationThe filtrate was concentrated under reduced pressure
  11. dry with materialdried over magnesium sulfate
  12. customThe solvent was removed under vacuum

Sources & evidence

ORD record
ord-74e0b51a6d064af894fcf690e01f97e6
Source dataset
uspto-grants-1994_01
Patent number
US05281612

Reaction notes

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