Hydrochloric Acid → Methyl 4-(hydroxymethyl)piperidine-1-carboxylate

Temperature

0 °C

4-Hydroxymethylpiperidine (1.0 g, 8.6 mmol) was dissolved in water (15 mL) and cooled to 0° C. To this solution was added dropwise a solution of potassium carbonate (4.8 g, 34.7 mmol) in water (10 mL), followed by methyl chloroformate (2.68 mL, 34.7 mmol). The mixture was stirred vigorously and allowed to warm to room temperature over 2 h. After stirring overnight (16 h), the reaction mixture was acidified with 6M aqueous hydrochloric acid and extracted with dichloromethane (3×60 mL). The extracts were combined, dried over sodium sulfate and filtered. The filtrate was evaporated to yield the title intermediate (1.4 g, 8.1 mmol, 93%) as a colorless oil. (m/z): C8H15NO3 calcd. 173.11. found 156.2 [M−H2O+H]+. 1H NMR (300 MHz, DMSO-d6): δ (ppm) 0.98 (m, 2H), 1.52 (m, 1H), 1.63 (br d, 2H), 2.72 (br m, 2H), 3.23 (d, 2H), 3.56 (s, 3H), 3.95 (br d, 2H), 4.48 (br s, 1H).

1. temperatureto warm to room temperature over 2 h
2. stirringAfter stirring overnight (16 h)
3. extractionextracted with dichloromethane (3×60 mL)
4. dry with materialdried over sodium sulfate
5. filtrationfiltered
6. customThe filtrate was evaporated

ORD record

ord-ee6f03ca4ef440e7b47432afafb18026

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09428489B2