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

HRID 219802

Reaktionsgleichung

Reaktionsgleichung von HRID 219802
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]

Komponenten

7

Edukt 3

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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittel2×HCID 6228DimethylformamideLösungsmittelHCID 8028TetrahydrofuranLösungsmittel

Reaktionsbedingungen

Temperatur
50 °C

Versuchsvorschrift

A mixture of ethyl 4-fluoro-3-nitrobenzoate (Clontech 01072, 25 g; 117.28 mmol; 1 eq.) and 2-methylpiperidine (41.54 mL; 351.84 mmol; 3 eq.) in DMF (100 mL) was heated to 50° C. for 2 hours The reaction was cooled to RT and diluted with water (100 mL), extracted with EtOAc, dried over MgSO4 and concentrated giving a yellow oil. The residue was taken up in THF (250 mL) and lithium hydroxide (14.04 g; 586.41 mmol; 5 eq.) was added followed by water (250 mL). The reaction mixture was stirred at RT for 2 days. After evaporation of 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 affording the title compound as a yellow solid (24.81 g, 80%). 1H NMR (DMSO-d6, 300 MHz) δ 13.09 (br s, 1H), 8.23-8.22 (d, J=2.14 Hz, 1H), 8.04-8.01 (dd, J=8.72 Hz, 2.19 Hz, 1H), 7.44-7.41 (d, J=8.94 Hz, 1H), 3.63-3.61 (m, 1H), 3.22-3.18 (m, 1H), 2.89-2.85 (m, 1H), 1.78-1.44 (m, 6H), 1.06-1.04 (d, J=6.65 Hz, 3H). LC/MS (Method B): 265.2 (M+H)+; 263.2 (M+H)−. HPLC (Method A) Rt 3.96 min (Purity: 97.9%)

Aufarbeitung

  1. temperaturewas cooled to RT
  2. extractionextracted with EtOAc
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated
  5. customgiving a yellow oil
  6. customAfter evaporation of THF
  7. additionthe solution was diluted with water
  8. washwashed with Et2O
  9. extractionextracted with Et2O
  10. dry with materialdried over MgSO4
  11. concentrationconcentrated

Quellen und Nachweise

ORD-Eintrag
ord-3c10a4430ca64e25bcebfe743e97de1c
Quelldatensatz
uspto-grants-2012_06
Patentnummer
US08202865B2

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