Aluminium lithium hydride → (1-Benzylazepan-3-yl)methanol

HRID 1246918Notes

Reaction equation

HRID 1246918 reaction equation
C[O:2][C:3]([CH:5]1[CH2:11][CH2:10][CH2:9][CH2:8][N:7]([CH2:12][C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=2)[C:6]1=O)=O.[H-].[H-].[H-].[H-].[Li+].[Al+3]>C1COCC1>[NH3:7].[CH2:12]([N:7]1[CH2:8][CH2:9][CH2:10][CH2:11][CH:5]([CH2:3][OH:2])[CH2:6]1)[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1

Participants

5

Reactant 2

HCID 21226445Aluminium lithium hydrideHCID 21902024Methyl 1-benzyl-2-oxoazepane-3-carboxylate

Product 2

HCID 222AmmoniaHCID 21901990(1-Benzylazepan-3-yl)methanolYield 117.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

1-Benzyl-2-oxo-azepan-2-carboxylic acid methyl ester (143) (0.2154 g, 0.8243 mmol) dissolved in anhydrous THF (2.9 mL) was added to a stirring suspension of LiAlH4 in THF (1.5 mL) over approx. 1.5 hours. The reaction mixture was stirred overnight. The reaction was judged complete by TLC and was quenched by the sequential addition of H2O (0.4 mL), then 2N NaOH (1.0 mL) and H2O (0.4 mL). The mixture was stirred at room temperature for 30 minutes, then was filtered, dried with Na2SO4, and concentrated in vacuo. Crude material was purified by automated silica gel chromatography with 15:85:5 CH2Cl2:Hexanes:2N NH3 in EtOH to obtain 0.1062 g (59%) of pure (1-benzyl-azepan-3-yl)-methanol (144). 1H NMR (CDCl3) 7.40–7.23 (5H, m), 3.65 (2H, s), 3.54 (1H, dd, J=10.4, 3.5 Hz), 3.43 (1H, dd, J=10.4, 5.4 Hz), 2.82 (1H, J=13.3, 3.1Hz), 2.77 (2H, m), 2.44 (1H, ddd, J=12.2, 8.6, 3.3 Hz), 1.90–1.45 (6H, m) ppm. 13C NMR (CDCl3, 75 MHz) 139.14, 128.97, 128.14, 126.91, 67.20, 63.85, 58.49, 56.87, 39.59, 29.68, 29.43, 25.23 ppm. LRMS: 219.64.

Workup

  1. customwas quenched by the sequential addition of H2O (0.4 mL)
  2. stirringThe mixture was stirred at room temperature for 30 minutes
  3. filtrationwas filtered
  4. dry with materialdried with Na2SO4
  5. concentrationconcentrated in vacuo
  6. customCrude material was purified by automated silica gel chromatography with 15:85:5 CH2Cl2

Sources & evidence

ORD record
ord-62c5774843e14b8784874e5f90fab369
Source dataset
uspto-grants-2006_10
Patent number
US07129228B2

Reaction notes

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