Sodium Bicarbonate → HCID 23361310, compound

HRID 1742238Notes

Reaction equation

HRID 1742238 reaction equation
[N:1]1([CH2:7][CH2:8][N:9]2[CH2:13][CH2:12][CH2:11][CH:10]2[C:14]2[CH:19]=[CH:18][C:17]([O:20]C)=[CH:16][CH:15]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1.C(=O)(O)[O-].[Na+]>Br>[N:1]1([CH2:7][CH2:8][N:9]2[CH2:13][CH2:12][CH2:11][CH:10]2[C:14]2[CH:15]=[CH:16][C:17]([OH:20])=[CH:18][CH:19]=2)[CH2:6][CH2:5][O:4][CH2:3][CH2:2]1

Participants

4

Reactant 2

HCID 516892Sodium BicarbonateHCID 23361260HCID 23361260, compound

Product 1

HCID 23361310HCID 23361310, compoundYield 66.1%

Reagents, catalysts & solvents 1

HCID 260Hydrogen BromideSolvent

Conditions

Temperature
110 °C

Procedure

To a suspension of pentane washed sodium hydride (80% oil dispersion, 2.51 g) in dry dimethylformamide (50 ml) was added 2-(4-methoxyphenyl)pyrrolidine (6.74 g) in dimethylformamide (80 ml), followed by N-(2-chloroethyl)morpholine hydrochloride (7.23 g) and potassium iodide (0.05 g) at ambient temperature. The solution was heated at 110° C. for 1.5 hrs, cooled to ambient temperature, and quenched with saturated aqueous ammonium chloride solution. The mixture was distilled through a Kugelrohr apparatus. The residue was diluted with water and ethyl acetate. The layers were separated, and the aqueous phase was extracted with ethyl acetate (4 times). The combined organic extracts were washed with brine, dried over anhydrous potassium carbonate, filtered, and the filtrate was concentrated. The residue was purified by flash column chromatography (silica gel, 2% triethylamine/1% methanol/ethyl acetate). The appropriate fractions were collected and concentrated to afford 3.99 g (34.6%) of 1-[2-(4-morpholinyl)ethyl]-2-(4-methoxyphenyl)pyrrolidine. 1-[2-(4-Morpholinyl)ethyl]-2-(4-methoxyphenyl)pyrrolidine (3.75 g) was dissolved in 48% hydrobromic acid (35 ml) and warmed at 110° C. for 5 hrs. The reaction mixture was cooled, neutralized with saturated sodium bicarbonate solution and extracted into dichloromethane (6 times). The combined organic extracts were washed with brine, dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The residue was purified by flash column chromatography. The appropriate fractions were collected and concentrated to afford 2.36 g (66.0%) of product. The analytical sample was recrystallized from ether/petroleum ether and had mp 107°-108° C.

Workup

  1. temperatureThe reaction mixture was cooled
  2. extractionextracted into dichloromethane (6 times)
  3. washThe combined organic extracts were washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationfiltered
  6. concentrationthe filtrate was concentrated
  7. customThe residue was purified by flash column chromatography
  8. customThe appropriate fractions were collected
  9. concentrationconcentrated

Sources & evidence

ORD record
ord-b3fcd6ee9d474e5aaf6d97bd29431267
Source dataset
uspto-grants-1994_08
Patent number
US05338739

Reaction notes

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