Diethyl Malonate → Diethyl 2-(3-nitropyridin-4-yl)malonate

HRID 840929노트

반응식

HRID 840929 반응식
[H-].[Na+].[C:3]([O:11][CH2:12][CH3:13])(=[O:10])[CH2:4][C:5]([O:7][CH2:8][CH3:9])=[O:6].Cl[C:15]1[CH:20]=[CH:19][N:18]=[CH:17][C:16]=1[N+:21]([O-:23])=[O:22]>C1(C)C=CC=CC=1>[CH2:12]([O:11][C:3](=[O:10])[CH:4]([C:15]1[CH:20]=[CH:19][N:18]=[CH:17][C:16]=1[N+:21]([O-:23])=[O:22])[C:5]([O:7][CH2:8][CH3:9])=[O:6])[CH3:13]

참가 물질

5

반응물 3

HCID 7761Diethyl MalonateHCID 24758Sodium hydrideHCID 27357814-Chloro-3-nitropyridine

생성물 1

HCID 12244207Diethyl 2-(3-nitropyridin-4-yl)malonate수율 18.2%

시약·촉매·용매 1

HCID 1140Toluene용매2회

실험 절차

To a suspension of 3.05 g of 60% sodium hydride (76.0 mmol) in toluene (50 mL) in a 250 mL RB flask was added 12.2 g of diethyl malonate (76.0 mmol) dropwise. The reaction mixture was stirred for 30 min under nitrogen, and a solution of 10.8 g of 4-chloro-3-nitropyridine (prepared according to the procedure of Houston et al. J. Med. Chem. 1985, 28, 467) in toluene (50 mL) was added dropwise and the resulting mixture refluxed for 4 hours. The reaction mixture was concentrate, and the residue was partitioned between 100 mL each of dilute hydrochloric acid and diethyl ether. The aqueous phase was extracted twice with 100 mL of ether, and the combined ether phases were dried over magnesium sulfate and concentrated to give a dark oil. This was chromatographed on silica gel eluting with a hexane-30% hexane/EtOAc gradient to give 3.5 g of the title compound as a colorless oil which crystallized on standing. 1H NMR (DMSO-d6): δ1.15 (t, J=7.1 Hz, 6H), 4.16 (q, J=7.1 Hz, 4H), 5.55 (s, 1H), 7.59 (d, J=5.1 Hz, 1H), 8.89 (d, J=5.1 Hz, 1H), 9.24 (s, 1H); C12H14N2O6: APES−MS m/z 281 (M−H).

후처리

  1. temperaturethe resulting mixture refluxed for 4 hours
  2. concentrationThe reaction mixture was concentrate
  3. customthe residue was partitioned between 100 mL each of dilute hydrochloric acid and diethyl ether
  4. extractionThe aqueous phase was extracted twice with 100 mL of ether
  5. dry with materialthe combined ether phases were dried over magnesium sulfate
  6. concentrationconcentrated
  7. customto give a dark oil
  8. customThis was chromatographed on silica gel eluting with a hexane-30% hexane/EtOAc gradient

출처 및 근거

ORD 기록
ord-ac808cab2ab4492c8009737fa64332fb
출처 데이터셋
uspto-grants-2002_04
특허 번호
US06369086B1

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