Methanol → HCID 45139441, compound

Temperature

0 °C

A 1M solution of borane complex in THF (2.25 mL, 2.25 mmol) was added to a cooled solution (0° C.) of 4-tert-butoxycarbonylamino-4-carbamoyl-piperidine-1-carboxylic acid tert-butyl ester (107 mg, 0.3 mmol) in THF (4.3 mL). After stirring for 5 minutes at 0° C. the reaction mixture was allowed to warm to room temperature. The reaction mixture was further warmed to 60° C. and stirred overnight. The reaction mixture was cooled to room temperature and methanol (5.1 mL) was added. After stirring for 30 minutes, the solvents were removed by evaporation. The reaction mixture was partitioned between an aqueous saturated solution of ammonium chloride (10 mL) and dichloromethane (10 mL). After further extraction of the aqueous phase with dichloromethane (20 mL), the combined organic phases were dried (Mg2SO4), filtered and concentrated. Flash column chromatography on silica, eluting with 5% methanol in dichloromethane, gave 4-aminomethyl-4-tert-butoxycarbonylamino-piperidine-1-carboxylic acid tert-butyl ester (5.5 mg, 0.017 mmol, 6%). LC-MS (LCT2) m/z 352 [M+Na+], Rt 7.16 min.

1. temperatureto warm to room temperature
2. temperatureThe reaction mixture was further warmed to 60° C.
3. stirringstirred overnight
4. temperatureThe reaction mixture was cooled to room temperature
5. stirringAfter stirring for 30 minutes
6. customthe solvents were removed by evaporation
7. customThe reaction mixture was partitioned between an aqueous saturated solution of ammonium chloride (10 mL) and dichloromethane (10 mL)
8. extractionAfter further extraction of the aqueous phase with dichloromethane (20 mL)
9. dry with materialthe combined organic phases were dried (Mg2SO4)
10. filtrationfiltered
11. concentrationconcentrated
12. washFlash column chromatography on silica, eluting with 5% methanol in dichloromethane

ORD record

ord-b16bbe0380bc4393bc5f78b7ed92a4c0

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08809336B2