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

HRID 393343

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HRID 393343 반응식
[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

참가 물질

5

반응물 4

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

생성물 1

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

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온도
50 °C

실험 절차

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).

후처리

  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%

출처 및 근거

ORD 기록
ord-77510a1604e548068113d3b093e691b9
출처 데이터셋
uspto-grants-2004_10
특허 번호
US06806287B2

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