4-(1-Benzylpiperidin-4-yl)butan-1-ol synthesis

12synthesis methods

Product Name:4-(1-Benzylpiperidin-4-yl)butan-1-ol
CAS Number:318508-02-0
Molecular formula:C16H25NO
Molecular Weight:247.38

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Yield:318508-02-0 65%

Reaction Conditions:

with N-ethyl-N,N-diisopropylamine in acetonitrile at 105; for 1 h;

Steps:

16 4.1.16
1-Benzyl-4-(4-hydroxybutyl)piperidine (26)

In two 20-mL pressure vials (20 bar) amine 25 (2 * 4.0 g, 2 * 25.45 mmol) was dissolved in acetonitrile (2 * 10 mL) under warming.
Diisopropylethylamine (2 * 3.62 g, 2 * 28.0 mmol) and benzyl bromide (2 * 4.78 g, 2 * 28.0 mmol) were added under stirring and the mixture was heated in a bath at 105 °C for 60 min.
The solvent was removed under reduced pressure and the residue taken up in CH₂Cl₂ (250 mL) and 5% aq NaOH (150 mL).
The mixture was vigorously shaken, the phases were separated, and the aqueous phase treated with CH₂Cl₂ (100 mL).
The CH₂Cl₂ extracts were combined, washed with water (50 mL) and dried over Na₂SO₄.
The solvent was removed under reduced pressure and the product was purified by column chromatography (eluent: CH₂Cl₂ to CH₂Cl₂/MeOH 10:1).
Amino alcohol 26 was obtained as an orange oil (8.2 g, 65%). R_f = 0.5 (CH₂Cl₂/MeOH 5:1). IR (neat) 3330 br, 2925, 1495, 1455 cm^-1. ¹H NMR (300 MHz, CD₃OD) δ (ppm) 1.17-1.33 (m, 5H), 1.34-1.46 (m, 2H), 1.48-1.59 (m, 2H), 1.72 (br d, 2H, J 9.6 Hz), 2.03 (br t, 2H, J 11.3 Hz), 2.92 (br d, 2H, J 11.8 Hz), 3.54 (s, 2H), 3.56 (t, 2H, J 6.5 Hz), 7.26-7.37 (m, 5H).
¹³C NMR (75 MHz, CD₃OD) δ (ppm) 24.9, 33.8, 34.7, 37.6, 38.3, 55.7, 63.8, 65.3, 129.3, 130.1, 131.8, 139.0. MS (ESI, MeOH) m/z (%) 270 (7) [M+Na]⁺, 248 (100) [M+H]⁺. C₁₆H₂₅NO (247.4).

References:

Keller, Max;Tr?nkle, Christian;She, Xueke;Pegoli, Andrea;Bernhardt, Günther;Buschauer, Armin;Read, Roger W. [Bioorganic and Medicinal Chemistry,2015,vol. 23,# 14,p. 3970 - 3990]