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

A stirred solution of 4-hydroxymethylpiperidine (2.0 g, 17.4 mmol) in dry dichloromethane (DCM, 100 mL) was cooled to 0° C., treated with triethylamine (4.8 mL, 34.8 mmol) followed by benzyl chloroformate (3.7 mL, 34.8 mmol), allowed to warm to room temperature and stirred for two hours. The mixture was partitioned between DCM (50 mL) and water (30 mL). The layers were separated and the aqueous phase was extracted with DCM (2×50 mL). The combined organic phases were washed with brine (1×30 mL), dried over Na2SO4 and evaporated to a residue, that was purified by column chromatography using a gradient of 70 to 100% EtOAc in hexanes as eluant to give 3.85 g (89%) of E-12 as clear oil: 1H NMR (CDCl3) δ 1.17 (m, 2H), 1.72 (m, 3H), 2.15 (br s, 1H), 2.78 (t, 2H, J=12.24), 3.47 (d, 2H, J=6.04), 4.20 (d, 2H, J=11.68), 5.12 (s, 2H), 7.33 (m, 5H).

1. customThe mixture was partitioned between DCM (50 mL) and water (30 mL)
2. customThe layers were separated
3. extractionthe aqueous phase was extracted with DCM (2×50 mL)
4. washThe combined organic phases were washed with brine (1×30 mL)
5. dry with materialdried over Na2SO4
6. customevaporated to a residue, that
7. customwas purified by column chromatography
8. customto give 3.85 g (89%) of E-12 as clear oil

ORD record

ord-cdd472fd020a4bf99cc7e998b1389546

Source dataset

uspto-grants-2009_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07572913B2