1-Benzyl-5-(hydroxyMethyl)piperidin-2-one

1-Benzyl-5-(hydroxyMethyl)piperidin-2-one Property

Boiling point:

422.3±28.0 °C(Predicted)

Density 

1.148±0.06 g/cm3(Predicted)

storage temp. 

Sealed in dry,Room Temperature

pka

14.73±0.10(Predicted)

Hazard and Precautionary Statements (GHS)

1-Benzyl-5-(hydroxyMethyl)piperidin-2-one Chemical Properties,Usage,Production

Uses

1-Benzyl-5-(hydroxymethyl)piperidin-2-one is used as a reactant in the synthesis of (±)-cytisine.

Synthesis

General procedure for the synthesis of 1-benzyl-5-(hydroxymethyl)piperidin-2-one from methyl 1-benzyl-6-oxopiperidine-3-carboxylate: the compound methyl 1-benzyl-6-oxopiperidine-3-carboxylate (5.23 g, 23.85 mmol) was dissolved in anhydrous THF (35 mL) and cooled down to 0 °C. LiBH4 (1.04 g, 47.70 mmol) was added under stirring, followed by slowly warming the reaction mixture to room temperature and stirring overnight. Upon completion of the reaction, the reaction was quenched with water (20 mL) at 0 °C, followed by the addition of 10% HCl solution to adjust the pH. The aqueous layer was extracted with EtOAc (4 x 20 mL), the organic layers were combined, dried with anhydrous MgSO4, filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography (eluent: cyclohexane/EtOAc, 60:40) to afford 1-benzyl-5-(hydroxymethyl)piperidin-2-one (4.03 g, 77% yield) as a clear oil (Rf = 0.11, cyclohexane/EtOAc, 50:50).1H NMR (600 MHz, CDCl3) δ 7.33-7.18 ( m, 5H, PhH), 4.59 (d, J = 14.6 Hz, 1H, PhCH2), 4.53 (d, J = 14.6 Hz, 1H, PhCH2), 3.53 (ddd, J = 10.7, 5.6 Hz, 1H, CH2OH), 3.44 (ddd, J = 10.7, 7.2 Hz, 1H, CH2OH), 3.30 ( ddd, J = 12.2, 5.2, 1.5 Hz, 1H, NCH2), 2.99 (dd, J = 12.2, 10.1 Hz, 1H, NCH2), 2.92 (br s, 1H, OH), 2.51 (ddd, J = 17.8, 5.8, 3.4 Hz, 1H, C=OCH2), 2.39 (ddd, J = 17.8, 11.3, 6.5 Hz, 1H, C=OCH2), 2.39 (dd, J = 17.8 11.3, 6.5 Hz, 1H, C=OCH2), 2.04-1.95 (m, 1H, OHCH2CH), 1.89-1.82 (m, 1H, C=OCH2CH2), 1.54-1.46 (m, 1H, C=OCH2CH2); 13C NMR (151 MHz, CDCl3) δ 170.0, 137.0 , 128.5, 127.9, 127.3, 64.3, 50.3, 49.8, 36.4, 31.1, 23.8; HRMS (ES) m/z calcd for C13H18NO2 [M+H]+ 220.1338, found 220.1329.

References

[1] Chemistry - A European Journal, 2006, vol. 12, # 32, p. 8208 - 8219
[2] Amino Acids, 2013, vol. 44, # 2, p. 511 - 518
[3] Patent: WO2017/100776, 2017, A1. Location in patent: Paragraph 0143; 0145
[4] Patent: WO2018/160889, 2018, A1. Location in patent: Page/Page column 453; 454
[5] Organic and Biomolecular Chemistry, 2004, vol. 2, # 13, p. 1825 - 1826