Triethylamine → Ethyl 4-(hydroxymethyl)piperidine-1-carboxylate

Temperature

0 °C

1.0 equivalent 4-piperidinemethanol (D1) (10.00 g, 86.8 mmol) was dissolved in dichloromethane (350 mL), cooled in an ice-H2O bath and treated dropwise with a solution of 1.05 equivalents ethyl chloroformate (9.89 g, 91.1 mmol) in dichloromethane (50 mL), followed by the dropwise addition of a solution of 1.0 equivalents triethylamine (8.78 g) in dichloromethane (50 mL). The reaction was stirred at ≈0° C. for 15 min, then at room temperature for 10 min. The reaction was diluted with dichloromethane (250 mL) and washed successively with (150 mL each) H2O, 0.1 N HCl (aq) (×2), saturated brine, then dried (Na2SO4) and filtered. The filtrate was concentrated in vacuo to give ethyl 4-(hydroxymethyl)-piperidine-1-carboxylate (D2) as a viscous, pale bluish-green oil. 1H-NMR (400 MHz, CDCl3) δ 4.15 (br m, 2H), 4.09 (q, J=7.1 Hz, 2H), 3.46 (d, J=6.4 Hz, 2H), 2.72 (br t, J=12.4 Hz, 2H), 2.07 (s, 1H), 1.70 (m, 2H), 1.63 (m, 1H), 1.23 (t, J=7.2 Hz, 3H), 1.12 (m, 2H); tR=1.56 min [10-99% CH3CN gradient over 5 mins with 0.1% TFA (aq)]; Theoretical (M+H)+ m/z for C9H17NO3=188.1; Found 188.0.

1. temperaturecooled in an ice-H2O bath
2. waitat room temperature for 10 min
3. washwashed successively with (150 mL each) H2O, 0.1 N HCl (aq) (×2), saturated brine
4. dry with materialdried (Na2SO4)
5. filtrationfiltered
6. concentrationThe filtrate was concentrated in vacuo

ORD record

ord-ba1fa1f5c99f4e48af58ae27db976dc2

Source dataset

uspto-grants-2012_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08263605B2