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-8ae5794b45d5428e8e79853bf229ad2f

Source dataset

uspto-grants-2009_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07622587B2