Ethyl (3S)-piperidine-3-carboxylate → HCID 58374092, compound

HRID 1948480Notes

Reaction equation

[O:1]1[CH2:3][C@@H:2]1[C:4]1[CH:11]=[CH:10][C:7]([C:8]#[N:9])=[CH:6][CH:5]=1.[NH:12]1[CH2:17][CH2:16][CH2:15][C@H:14]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:13]1>CN(C)C1C=CN=CC=1.CC(O)C>[C:8]([C:7]1[CH:10]=[CH:11][C:4]([C@H:2]([OH:1])[CH2:3][N:12]2[CH2:17][CH2:16][CH2:15][C@H:14]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH2:13]2)=[CH:5][CH:6]=1)#[N:9]

Participants

Conditions

Temperature: 55 °C

Procedure

(S)-4-(Oxiran-2-yl)benzonitrile (10.00 g, 68.9 mmol), (S)-ethyl piperidine-3-carboxylate (10.83 g, 68.9 mmol) and iPrOH (100 mL) was charged into a round bottom flask under N2. After heating at 55° C. for 4 hours, 4-dimethylaminopyridine (1.683 g, 13.78 mmol) was then added. The reaction mixture was then heated to 50° C. for an additional 12 hours. At this time HPLC indicated the starting material was completely converted to the desired product. The reaction mixture was then cooled to room temperature. EtOAc (120 ml) was added, followed by 100 ml of water. The organic layer was separated, extracted with EtOAc (2×100 mL) and concentrated under vacuo to give a crude product. The crude product was recrystallized from EtOH/EtOAc/H2O (3/2/2) (8 ml/1 g) to give a crystalline off-white solid 14A-alt (15 g, 72% yield, 99.6% e.e.). The absolute and relative stereochemistry was determined by single X-ray crystallography employing a wavelength of 1.54184 Å. The crystalline material had an orthorhombic crystal system and unit cell parameters approximately equal to the following:

Workup

temperatureThe reaction mixture was then heated to 50° C. for an additional 12 hours

Sources & evidence

ORD record: ord-9475bce491604652a222db2108dde47d
Source dataset: uspto-grants-2013_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08399451B2

Reaction notes

Loading…