Lithium Hydroxide → 4-(2-Methylpiperidin-1-yl)-3-nitrobenzoic acid

HRID 219817노트

반응식

HRID 219817 반응식
F[C:2]1[CH:12]=[CH:11][C:5]([C:6]([O:8]CC)=[O:7])=[CH:4][C:3]=1[N+:13]([O-:15])=[O:14].[CH3:16][CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][NH:18]1.[OH-].[Li+]>CN(C=O)C.O.C1COCC1>[CH3:16][CH:17]1[CH2:22][CH2:21][CH2:20][CH2:19][N:18]1[C:2]1[CH:12]=[CH:11][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[N+:13]([O-:15])=[O:14]

참가 물질

7

반응물 3

HCID 3939Lithium HydroxideHCID 79742-MethylpiperidineHCID 21277355Ethyl 4-fluoro-3-nitrobenzoate

생성물 1

HCID 431767024-(2-Methylpiperidin-1-yl)-3-nitrobenzoic acid수율 80%

시약·촉매·용매 3

HCID 962Water용매HCID 6228Dimethylformamide용매HCID 8028Tetrahydrofuran용매

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온도
50 °C

실험 절차

A mixture of ethyl 4-fluoro-3-nitrobenzoate (25 g; 117.28 mmol) and 2-methylpiperidine (41.54 mL; 351.84 mmol) in DMF (100 mL) was heated to 50° C. for 2 h. The reaction was allowed to cool to RT and diluted with water (100 mL). Extraction with EtOAc, drying over sodium sulfate and concentration under vacuum gave a yellow oil that was taken up in THF (250 mL) followed by the addition of an aqueous solution of lithium hydroxide (14.0 g; 586.4 mmol, 2.3 M). The reaction mixture was stirred at RT for 48 h. After evaporation of the THF, the solution was diluted with water and washed with Et2O. The aqueous layer was acidified to pH 5 with AcOH, extracted with Et2O, dried over MgSO4 and concentrated under vacuum to give the title compound as a yellow solid (24.8 g, 80%). 1H NMR (DMSO-d6, 300 MHz) δ 13.1 (bs, 1H), 8.23 (d, J=2 Hz, 1H), 8.02 (dd, J=8.7, 2 Hz, 1H), 7.41 (d, J=8.7 Hz, 1H), 3.63-3.61 (m, 1H), 3.23-3.18 (m, 1H), 2.89-2.85 (m, 1H), 1.79-1.54 (m, 6H), 1.47 (d, J=6 Hz, 3H). LC/MS (Method B): 265.2 (M+H)+. HPLC (Method A) Rt 3.96 min (Purity: 97.9%).

후처리

  1. temperatureto cool to RT
  2. extractionExtraction with EtOAc
  3. dry with materialdrying over sodium sulfate and concentration under vacuum
  4. customgave a yellow oil that
  5. customAfter evaporation of the THF
  6. additionthe solution was diluted with water
  7. washwashed with Et2O
  8. extractionextracted with Et2O
  9. dry with materialdried over MgSO4
  10. concentrationconcentrated under vacuum

출처 및 근거

ORD 기록
ord-a83ef59504b1428fbb938d657077a40f
출처 데이터셋
uspto-grants-2012_06
특허 번호
US08202865B2

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