Potassium Carbonate → 2-(3-Methoxyphenyl)-1-(2-pyridinylmethyl)pyrrolidine

HRID 233031Notes

Reaction equation

HRID 233031 reaction equation
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]2[CH2:13][CH2:12][CH2:11][NH:10]2)[CH:6]=[CH:7][CH:8]=1.C(=O)([O-])[O-].[K+].[K+].Cl.[N:21]1[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=1[CH2:27]Cl>C(#N)C>[CH3:1][O:2][C:3]1[CH:4]=[C:5]([CH:9]2[CH2:13][CH2:12][CH2:11][N:10]2[CH2:27][C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][N:21]=2)[CH:6]=[CH:7][CH:8]=1

Participants

5

Reactant 3

HCID 11430Potassium CarbonateHCID 23392Picolyl chloride hydrochlorideHCID 36138242-(3-Methoxyphenyl)pyrrolidine

Product 1

HCID 233612632-(3-Methoxyphenyl)-1-(2-pyridinylmethyl)pyrrolidineYield 91%

Reagents, catalysts & solvents 1

HCID 6342AcetonitrileSolvent

Procedure

To a solution of 2-(3-methoxyphenyl)pyrrolidine (3.0 g) in dry acetonitrile (70 ml) was added milled potassium carbonate (6.1 g) followed by 2-picolyl chloride hydrochloride (3.1 g) at ambient temperature, under nitrogen, with stirring for 65 hrs. The reaction mixture was filtered through a pad of celite, and the filter cake was washed with ethyl acetate. The combined filtrates were concentrated and the residue was purified by flash column chromatography (silica gel, 5% methanol/ether). The appropriate fractions were collected and concentrated to give 4.1 g (91%) of 2-(3-methoxyphenyl)-1-(2-pyridinylmethyl)pyrrolidine. 2-(3-Methoxyphenyl)-1-(2-pyridinylmethyl)pyrrolidine and 48% hydrobromic acid (40 ml) were warmed to 100° C. for 7 hrs, cooled to ambient temperature, and neutralized with saturated sodium bicarbonate solution. The mixture was extracted with dichloromethane (2 times). The combined organic extracts were dried over anhydrous sodium sulfate, filtered, and the filtrate was concentrated. The residue was purified by flash column chromatography (silica gel, 1:1 ethyl acetate/dichloromethane). The appropriate fractions were collected and concentrated to give 2.7 g (69%) of product, mp 96°-98° C.

Workup

  1. filtrationThe reaction mixture was filtered through a pad of celite
  2. washthe filter cake was washed with ethyl acetate
  3. concentrationThe combined filtrates were concentrated
  4. customthe residue was purified by flash column chromatography (silica gel, 5% methanol/ether)
  5. customThe appropriate fractions were collected
  6. concentrationconcentrated

Sources & evidence

ORD record
ord-abe4dc7be5dd4f3c986db96eb8435d7e
Source dataset
uspto-grants-1997_01
Patent number
US05591856

Reaction notes

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