Benzyl Bromide → 3-(benzyloxy)propan-1-amine

HRID 2354595Notes

Reaction equation

HRID 2354595 reaction equation
[H-].[Na+].[NH2:3][CH2:4][CH2:5][CH2:6][OH:7].[CH2:8](Br)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>C1COCC1>[CH2:8]([O:7][CH2:6][CH2:5][CH2:4][NH2:3])[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

5

Reactant 3

HCID 7498Benzyl BromideHCID 90863-Amino-1-propanolHCID 24758Sodium hydride

Product 1

HCID 71307843-(benzyloxy)propan-1-amineYield 8.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A 60% sodium hydride dispersion in mineral oil (4 g, 0.1 mol) in a small portion at room temperature was added to a stirred solution of 3-amino-1-propanol (7.51 g, 0.1 mol) in THF (150 mL). The mixture was stirred for 30 min under nitrogen, and benzyl bromide (11.9 mL, 0.1 mol) was added. The mixture was stirred for 10 h at room temperature, and concentrated in vacuo. The residue was partitioned between 1 N aqueous HCl solution and CH2Cl2. The aqueous layer was adjusted to pH 10 with 10% aqueous NaOH solution, and extracted with CH2Cl2 (3×100 mL). The extract was dried over MgSO4 and concentrated in vacuo. The residue was purified by silica gel column chromatography using CH2Cl2/MeOH (3:1 to 2:1, v/v) to give 3-(benzyloxy)propylamine (1.37 g, 8.3%) as a yellow oil. 1,3-Dicyclohexylcarbodiimide (14.4 mg, 0.07 mmol) in CH2Cl2 (2 mL) at 0° C. was added dropwise to a mixture of 5 (32 mg, 0.07 mmol) and 3-(benzyloxy)propylamine (11.6 mg, 0.07 mmol), and 1-hydroxybenzotriazole hydrate (9.5 mg, 0.07 mmol) in CH2Cl2 (5 mL). The reaction mixture was stirred for 18 h at room temperature and concentrated in vacuo. The residue was purified by silica gel column chromatography using CH2Cl2/MeOH (30:1, v/v) to afford 8 (36 mg, 85%) as a pale yellow liquid. 1H NMR (CDCl3) δ 8.05 (s, 1H, H4), 7.44 (d, 1H, H5, J=8.7 Hz), 7.19-7.28 (m, 11H, H6+2×OCH2Ph), 6.78-6.82 (m, 3H, H2′+H5′+H6′), 6.06 (AB, 2H, 3′,4′-OCH2O—, Δδ=6.9 Hz, J=1.5 Hz), 5.84 (AB, 2H, 7,8-OCH2O—, Δδ=4.2 Hz, J=1.5 Hz), 4.45 (s, 4H, 2×OCH2Pb), 4.38 (s, 2H, 2-CH2OBn), 3.55 (m, 4H, 3-CONHCH2CH2CH2OBn), 1.87 (quintet, 2H, 3-CONHCH2CH2CH2OBn. J=6.3 Hz); MS (FAB, positive) m/z 604 [M+H]+.

Workup

  1. stirringThe mixture was stirred for 10 h at room temperature
  2. concentrationconcentrated in vacuo
  3. customThe residue was partitioned between 1 N aqueous HCl solution and CH2Cl2
  4. extractionextracted with CH2Cl2 (3×100 mL)
  5. dry with materialThe extract was dried over MgSO4
  6. concentrationconcentrated in vacuo
  7. customThe residue was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-cc5536ba38ba42ccbbeb3d27f4dff625
Source dataset
uspto-grants-2010_07
Patent number
US07754718B2

Reaction notes

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