5-(2-(Tert-butoxycarbonyl)hydrazono)-5-(4-fluorophenyl)pentanoic acid → Tert-butyl 2-(4-fluorophenyl)-6-oxopiperidin-1-ylcarbamate
Reaction equation
[C:1]([O:5][C:6]([NH:8][N:9]=[C:10]([C:17]1[CH:22]=[CH:21][C:20]([F:23])=[CH:19][CH:18]=1)[CH2:11][CH2:12][CH2:13][C:14](O)=[O:15])=[O:7])([CH3:4])([CH3:3])[CH3:2]>[Pd].CO>[F:23][C:20]1[CH:21]=[CH:22][C:17]([CH:10]2[CH2:11][CH2:12][CH2:13][C:14](=[O:15])[N:9]2[NH:8][C:6](=[O:7])[O:5][C:1]([CH3:4])([CH3:3])[CH3:2])=[CH:18][CH:19]=1Participants
Procedure
Step AAG (2): 10% Palladium on carbon (0.5 g) was carefully added to a solution of 5-(2-(tert-Butoxycarbonyl)hydrazono)-5-(4-fluorophenyl)pentanoic acid (2.3 g, 7.09 mmol) in MeOH (30 mL) in a Parr hydrogenation bottle under nitrogen. The bottle was repeatedly evacuated and flushed with H2 gas (50 psi). The mixture was shaken for 5 h. The vessel was flushed with nitrogen. The reaction contents were filtered through diatomaceous earth (Celite®). The plug and vessel were washed with fresh methanol. The filtrates were combined and concentrated in vacuo. The crude product was purified using silica gel column chromatography (10-80, EtOAc/chloroform, linear gradient) to afford tert-butyl 2-(4-fluorophenyl)-6-oxopiperidin-1-ylcarbamate (1.2 g, 55% yield). 1H NMR (500 MHz, chloroform-d) δ ppm 7.13-7.20 (an, 2 H) 7.06 (t, J=8.55 Hz, 2 H) 6.40 (br. s., 1 H) 4.91 (br. s., 1 H) 2.52-2.75 (m, 2 H) 2.20-2.40 (m, 1 H) 1.77-1.93 (m, 3 H) 1.44 (s, 9 H).
Workup
- customThe bottle was repeatedly evacuated
- customflushed with H2 gas (50 psi)
- customThe vessel was flushed with nitrogen
- customThe reaction contents
- filtrationwere filtered through diatomaceous earth (Celite®)
- washThe plug and vessel were washed with fresh methanol
- concentrationconcentrated in vacuo
- customThe crude product was purified
Sources & evidence
- ORD record
- ord-2d753441dc3c47a698156e0846da5c66
- Source dataset
- uspto-grants-2013_01
- Patent number
- US08349880B2
Reaction notes
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