Dichloromethane → Methyl 4-(hydroxymethyl)piperidine-1-carboxylate

Temperature

5 °C

4-Hydroxymethylpiperidine (47.6 g, 1.0 eq) and water (300 mL) were charged to a flask. The resulting mixture was cooled to 0-10° C. Potassium carbonate (85.7 g, 1.5 eq) dissolved in water (150 mL) and methyl chloroformate (38.4 mL, 1.1 eq) were added while maintaining the temperature at below 10° C. When the addition was complete, the reaction mixture was warmed up to 20-30° C. for 1 hour. After the reaction was complete, dichloromethane (500 mL) was added to the reaction mixture. The organic layer was collected and washed with 1 M phosphoric acid solution (200 mL), saturated sodium bicarbonate solution (200 mL) and saturated sodium chloride solution (200 mL). The organic layer was dried over sodium sulfate (50 g, 1 w/w eq) and then distilled under vacuum to produce the title intermediate. (67.0 g, 90% yield)

1. temperaturewhile maintaining the temperature at below 10° C
2. additionWhen the addition
3. temperaturethe reaction mixture was warmed up to 20-30° C. for 1 hour
4. customThe organic layer was collected
5. washwashed with 1 M phosphoric acid solution (200 mL), saturated sodium bicarbonate solution (200 mL) and saturated sodium chloride solution (200 mL)
6. dry with materialThe organic layer was dried over sodium sulfate (50 g, 1 w/w eq)
7. distillationdistilled under vacuum

ORD record

ord-0fbbb6a231df4f91b16435917c5761c5

Source dataset

uspto-grants-2016_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09428489B2