Ammonia → (2R,4R)-1-tert-butyl 2-methyl 4-(3-(4-cyanophenyl)ureido)piperidine-1,2-dicarboxylate

4-isocyanatobenzonitrile (1.17 g, 8.13 mmol) was added to a solution of (2R,4R)-1-tert-butyl 2-methyl 4-aminopiperidine-1,2-dicarboxylate (2.0 g, 7.7 mmol) and NEt3 (1.3 mL, 9.3 mmol) in THF (30 mL), and the resulting solution was stirred at room temperature for 6 hours. 1M ammonia in methanol (5 mL) was then added to the reaction mixture to quench excess isocyanine. Water (100 mL) and ethyl acetate (200 mL) were added to the mixture. The organic layer was separated and dried over MgSO4 and concentrated to give a solid. Purification by Companion (ReadySep, 80 g, silica gel packed) using ethyl acetate/heptane from 40-70% as eluent provided the title compound as a white solid 2.9 g (90%). LC-MS: 403.2, 401.3 (t=2.6 min).

1. customto quench excess isocyanine
2. additionWater (100 mL) and ethyl acetate (200 mL) were added to the mixture
3. customThe organic layer was separated
4. dry with materialdried over MgSO4
5. concentrationconcentrated
6. customto give a solid
7. customPurification by Companion (ReadySep, 80 g, silica gel packed)

ORD record

ord-e3a1961d82b44dceae1a7b39a4a6341b

Source dataset

uspto-grants-2012_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08148401B2