Acetonitrile → Ethyl 2-[4-(3-chlorophenyl)-2-oxo-1-pyrrolidinyl]butanoate

HRID 1837632Notes

Reaction equation

HRID 1837632 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]2[CH2:12][NH:11][C:10](=[O:13])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1.Br[CH:15]([CH2:20][CH3:21])[C:16]([O:18][CH3:19])=[O:17].[H-].[Na+].[C:24](#N)C>>[Cl:1][C:2]1[CH:3]=[C:4]([CH:8]2[CH2:12][N:11]([CH:15]([CH2:20][CH3:21])[C:16]([O:18][CH2:19][CH3:24])=[O:17])[C:10](=[O:13])[CH2:9]2)[CH:5]=[CH:6][CH:7]=1

Participants

5

Reactant 4

HCID 6342AcetonitrileHCID 24758Sodium hydrideHCID 95577Butanoic acid, 2-bromo-, methyl esterHCID 179489414-(3-Chlorophenyl)pyrrolidin-2-one

Product 1

HCID 22387086Ethyl 2-[4-(3-chlorophenyl)-2-oxo-1-pyrrolidinyl]butanoate

Conditions

Temperature
50 °C

Procedure

In a 2 l three necked flask fitted with reflux condenser, magnetic stirrer and dropping funnel under inert atmosphere, 54.4 g (278 mmoles, 1 eq) of 4-(3-chlorophenyl)-2-pyrrolidinone 379 are dissolved in 1.4 l acetonitrile. 64 ml (100.7 g, 556 mmoles, 2 eq) of methyl 2-bromobutanoate are added and the temperature raised to 50° C. 22.24 g (556 mmoles, 2 eq) of sodium hydride are added by portions, the temperature raising to 65° C. The mixture is stirred one more hour at 50° C. The mixture is concentrated to dryness, the residue suspended in ethyl acetate, washed with water, the aqueous phase reextracted with ethyl acetate. The combined organic phases are dried over magnesium sulfate, filtered and concentrated to dryness. The residue is purified by PrepLC (1 kg SiO2, pet. ether/EtOAc, 70:30) to give 56.7 g of pure 380, 69%. 1H NMR (250 MHz, (CD3)2SO): 0.80-1.00 (m, 3H), 1.60-1.90 (2H, m), 2.35-255 (m, 1H: partially overlapped with solvent), 2.60-2.90 (m, 1H: partially overlapped with solvent), 3.70 (s, 3H), 3.50-3.80 (m, 3H), 4.50 (m, 1H), 7.20-7.50 (m, 4H).

Workup

  1. temperaturewith reflux condenser, magnetic stirrer
  2. temperaturethe temperature raising to 65° C
  3. concentrationThe mixture is concentrated to dryness
  4. washwashed with water
  5. dry with materialThe combined organic phases are dried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated to dryness
  8. customThe residue is purified by PrepLC (1 kg SiO2, pet. ether/EtOAc, 70:30)
  9. customto give 56.7 g of pure 380, 69%

Sources & evidence

ORD record
ord-3d4e8da6202e4e35875d4b1307f2e152
Source dataset
uspto-grants-2004_08
Patent number
US06784197B2

Reaction notes

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