Triethylamine → 4-(Aminomethyl)-1-benzylpiperidin-4-ol

To a pre-cooled solution (20° C.) of 1-benzyl-4-piperidone (35.0 mL, 196 mmol) and triethylamine (5.5 mL, 40 mmol) was added trimethylsilylcyanide (32.0 mL, 240 mmol), portionwise over 10 minutes. Once the addition was complete, the reaction mixture was stirred at room temperature for 3 hours. This reaction mixture was then cautiously added (10 mL portions over 12 minutes) to a stirring mixture of lithium aluminum hydride (8.5 g, 224 mmol) in tetrahydrofuran (420 mL). Once the addition was complete the reaction mixture was refluxed for 1.5 hours. After cooling to room temperature, the reaction was quenched with water (8.5 mL), followed by 1N NaOH (8.5 mL), and then water (2×8.5 mL). The resulting mixture was allowed to stir at room temperature overnight. The solids were filtered off and rinsed with DCM and ethanol. The filtrate was concentrated down to a solid and then purified by flash chromatography (0-20% methanol in DCM with 1% NH4OH) to give compound 397 as a yellow solid (39.7 g, 92%). LCMS-ESI (POS), M/Z, M+1: Found 221.2, Calculated 221.2.

1. additionOnce the addition
2. additionThis reaction mixture was then cautiously added (10 mL portions over 12 minutes)
3. additionOnce the addition
4. temperaturewas refluxed for 1.5 hours
5. temperatureAfter cooling to room temperature
6. customthe reaction was quenched with water (8.5 mL)
7. stirringto stir at room temperature overnight
8. filtrationThe solids were filtered off
9. washrinsed with DCM and ethanol
10. concentrationThe filtrate was concentrated down to a solid
11. custompurified by flash chromatography (0-20% methanol in DCM with 1% NH4OH)

ORD record

ord-096b4edfd7b84c0281d91f32439ea742

Source dataset

uspto-grants-2014_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08841312B2