Aluminium lithium hydride → N-(2-amino-4-fluorobenzyl)-1-benzylpiperidin-4-amine

HRID 501986Notes

Reaction equation

HRID 501986 reaction equation
[H-].[Al+3].[Li+].[H-].[H-].[H-].[CH2:7]([N:14]1[CH2:19][CH2:18][CH:17]([NH:20][C:21](=O)[C:22]2[CH:27]=[CH:26][C:25]([F:28])=[CH:24][C:23]=2[N+:29]([O-])=O)[CH2:16][CH2:15]1)[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1>O1CCOCC1>[NH2:29][C:23]1[CH:24]=[C:25]([F:28])[CH:26]=[CH:27][C:22]=1[CH2:21][NH:20][CH:17]1[CH2:18][CH2:19][N:14]([CH2:7][C:8]2[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=2)[CH2:15][CH2:16]1

Participants

4

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 59424284N-(1-Benzylpiperidin-4-yl)-4-fluoro-2-nitrobenzamide

Product 1

HCID 59424361N-(2-amino-4-fluorobenzyl)-1-benzylpiperidin-4-amineYield 100%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent2×

Procedure

To a solution of lithium aluminum hydride (4.01 g, 105.7 mmol) in anhydrous 1,4-dioxane (40 mL) at reflux was added N-(1-benzylpiperidin-4-yl)-4-fluoro-2-nitrobenzamide (9.87 g, 30.2 mmol) in anhydrous 1,4-dioxane (125 mL) dropwise under nitrogen over 30 minutes. The resulting mixture was heated at reflux for 3 h under nitrogen. After cooling to room temperature, the reaction was carefully quenched with ice water (10 mL), sodium hydroxide (50% in water, 50 mL), and extracted with diethyl ether (2×500 mL). The combined organic layers were washed with brine (100 mL), dried over magnesium sulfate, and concentrated in vacuo to afford the title compound (8.64 g, 100% yield) as a yellow oil, which was pure enough for use in the next step. 1H-NMR (CD3OD, 400 MHz) δ 7.52-7.40 (m, 5H), 7.28-7.18 (m, 1H), 6.53 (dd, J=11.2, 2.4, 1H), 6.48-6.38 (m, 1H), 4.33 (s, 2H), 4.18 (s, 2H), 3.68-3.46 (m, 3H), 3.25-3.10 (m, 2H), 2.50-2.42 (m, 2H), 2.16-1.93 (m, 2H). Mass spec.: 314.21 (MH+).

Workup

  1. temperatureThe resulting mixture was heated
  2. temperatureat reflux for 3 h under nitrogen
  3. customthe reaction was carefully quenched with ice water (10 mL), sodium hydroxide (50% in water, 50 mL)
  4. extractionextracted with diethyl ether (2×500 mL)
  5. washThe combined organic layers were washed with brine (100 mL)
  6. dry with materialdried over magnesium sulfate
  7. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-69e11706e5ee449a87dc75efe4624665
Source dataset
uspto-grants-2010_08
Patent number
US07772244B2

Reaction notes

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