Hydrochloric Acid → 1-(1-(benzyloxycarbonyl)piperidin-3-yl)-2-oxo-5-phenyl-2,3-dihydro-1H-imidazole-4-carboxylic acid

HRID 1685120Notes

Reaction equation

[Li+].[OH-].C([O:5][C:6]([C:8]1[NH:9][C:10](=[O:35])[N:11]([CH:19]2[CH2:24][CH2:23][CH2:22][N:21]([C:25]([O:27][CH2:28][C:29]3[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=3)=[O:26])[CH2:20]2)[C:12]=1[C:13]1[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=1)=[O:7])C.Cl>O1CCOCC1>[CH2:28]([O:27][C:25]([N:21]1[CH2:22][CH2:23][CH2:24][CH:19]([N:11]2[C:12]([C:13]3[CH:18]=[CH:17][CH:16]=[CH:15][CH:14]=3)=[C:8]([C:6]([OH:7])=[O:5])[NH:9][C:10]2=[O:35])[CH2:20]1)=[O:26])[C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1

Participants

Conditions

Temperature: 55 °C

Procedure

(2.6 g, 5.78 mmol) prepared in the previous step was combined with 26 mL of dioxane and 29 mL of 1N LiOH. The mixture was heated at 55° C. overnight. After the disappearance of 16D as monitored by LC/MS, the reaction was cooled to RT and approximately 50 mL of 1N HCl was added directly. The aqueous mixture was extracted with ethyl acetate (3×40 mL), washed with brine, dried over MgSO4, and concentrated in vacuo to afford 1-(1-(benzyloxycarbonyl)piperidin-3-yl)-2-oxo-5-phenyl-2,3-dihydro-1H-imidazole-4-carboxylic acid as an oil (16E) (2.43 g, quantitative yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 1.13 (d, J=9.60 Hz, 1H) 1.25 (br. s., 1H) 1.61-1.77 (m, 2H) 2.60 (br. s., 1H) 3.25 (br. s., 1H) 3.84-4.00 (m, 2H) 4.99 (s, 2H) 7.27-7.47 (m, 10H) 7.92-7.97 (m, 1H) 10.79 (s, 1H) 12.43 (br. s., 1H). This was used in next step without purification. ESI-MS: m/z 422.3 (M+H)+.

Workup

custom(2.6 g, 5.78 mmol) prepared in the previous step
temperaturethe reaction was cooled to RT
extractionThe aqueous mixture was extracted with ethyl acetate (3×40 mL)
washwashed with brine
dry with materialdried over MgSO4
concentrationconcentrated in vacuo

Sources & evidence

ORD record: ord-ed33d2eafd0243d8ae8202c882970bcb
Source dataset: uspto-grants-2012_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08148367B2

Reaction notes

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