Sodium hydride → 2-(3-Fluoro-4-nitro-phenyl)-2-isobutyl-malonic acid Diethyl Ester

HRID 385346

반응식

HRID 385346 반응식
[CH2:1]([O:3][C:4](=[O:15])[CH:5]([CH2:11][CH:12]([CH3:14])[CH3:13])[C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH3:2].[H-].[Na+].[F:18][C:19]1[CH:24]=[C:23](F)[CH:22]=[CH:21][C:20]=1[N+:26]([O-:28])=[O:27]>CN(C=O)C>[CH2:1]([O:3][C:4](=[O:15])[C:5]([C:23]1[CH:22]=[CH:21][C:20]([N+:26]([O-:28])=[O:27])=[C:19]([F:18])[CH:24]=1)([CH2:11][CH:12]([CH3:13])[CH3:14])[C:6]([O:8][CH2:9][CH3:10])=[O:7])[CH3:2]

참가 물질

5

반응물 3

HCID 24758Sodium hydrideHCID 25047Diethyl isobutylmalonateHCID 679672,4-Difluoronitrobenzene

생성물 1

HCID 579956132-(3-Fluoro-4-nitro-phenyl)-2-isobutyl-malonic acid Diethyl Ester

시약·촉매·용매 1

HCID 6228Dimethylformamide용매2회

반응 조건

온도
0 °C

실험 절차

To a solution of 2-isobutylmalonic acid diethyl ester (75.0 g, 0.35 mol) in DMF (200 mL) was added sodium hydride (60% in mineral oil, 13.0 g, 0.57 mol) over 20 min. at 0° C. The reaction mixture was stirred at 0° C. for 0.5 h, then warmed to 25° C. The reaction mixture was cooled down to 0° C. again and a solution of 2,4-difluoronitro-benzene (50.0 g, 0.31 mol) in DMF (150 mL) was added dropwise at 0° C. The reaction mixture was stirred at 25° C. for 16 h. After cooling, the reaction mixture was poured into ice water (200 mL) and extracted with EtOAc (3×100 mL). The combined organic phases washed with water (3×100 mL), brine (100 mL), and dried (MgSO4). Evaporation of the solvent under reduced pressure gave a brown oil. The crude product (92.0 g, 82%) was used for the next step without purification. 1H NMR (300 MHz, CDCl3/TMS): δ 8.03 (t, J=8.4 Hz, 1H), 7.70 (dd, J=12.9, 1.7 Hz, 1H), 7.47 (d, J=8.5 Hz, 1H), 4.25-4.18 (m, 4H), 2.28 (d, J=6.3 Hz, 2H), 1.54-1.45 (m, 1H), 1.25 (t, J=7.0 Hz, 6H), 0.82 (d, J=7.0 Hz, 6H); 13C NMR (75 MHz, CDCl3/TMS): δ 169.2, 154.5 (d, 1JCF=263.1 Hz), 146.9 (d, unresolved), 125.3, 124.1 (d, 3JCF=3.6 Hz), 118.6 (d, 2JCF=23.3 Hz), 62.0, 60.3, 44.1, 24.7, 23.6, 13.9.

후처리

  1. temperaturewarmed to 25° C
  2. temperatureThe reaction mixture was cooled down to 0° C. again
  3. stirringThe reaction mixture was stirred at 25° C. for 16 h
  4. temperatureAfter cooling
  5. extractionextracted with EtOAc (3×100 mL)
  6. washThe combined organic phases washed with water (3×100 mL), brine (100 mL)
  7. dry with materialdried (MgSO4)
  8. customEvaporation of the solvent under reduced pressure
  9. customgave a brown oil
  10. customThe crude product (92.0 g, 82%) was used for the next step without purification

출처 및 근거

ORD 기록
ord-425de5699c1442b094275d958516fab9
출처 데이터셋
uspto-grants-2013_02
특허 번호
US08367863B2

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