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

HRID 453246

反応式

HRID 453246 の反応式
[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

参加物

5

反応物 4

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

生成物 1

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

反応条件

温度
50 °C

実験手順

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), 2.35-2.55 (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).

後処理

  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%

出典と根拠

ORDレコード
ord-2a29b81f85c348d7bfc1f11fdff5ada8
出典データセット
uspto-grants-2013_07
特許番号
US08492416B2

関連ノート

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