Ethanol → (2S,4R)-2-((1R,2S)-1-(ethoxycarbonyl)-2-vinylcyclopropylcarbamoyl)-4-(4-nitrobenzoyloxy)pyrrolidinium chloride

HRID 403413

Reaction equation

C(O)C.C([Cl:7])(=O)C.[CH2:8]([O:10][C:11]([C@@:13]1([NH:18][C:19]([C@@H:21]2[CH2:25][C@@H:24]([O:26][C:27](=[O:37])[C:28]3[CH:33]=[CH:32][C:31]([N+:34]([O-:36])=[O:35])=[CH:30][CH:29]=3)[CH2:23][N:22]2C(OC(C)(C)C)=O)=[O:20])[CH2:15][C@H:14]1[CH:16]=[CH2:17])=[O:12])[CH3:9]>CCOC(C)=O>[Cl-:7].[CH2:8]([O:10][C:11]([C@@:13]1([NH:18][C:19]([C@@H:21]2[CH2:25][C@@H:24]([O:26][C:27](=[O:37])[C:28]3[CH:29]=[CH:30][C:31]([N+:34]([O-:36])=[O:35])=[CH:32][CH:33]=3)[CH2:23][NH2+:22]2)=[O:20])[CH2:15][C@H:14]1[CH:16]=[CH2:17])=[O:12])[CH3:9]

Participants

Conditions

Temperature: 15 °C

Procedure

To a stirring solution of ethanol at 0° C., was added acetyl chloride (1.77 kg). The resulting solution was aged for 30 min. (2S,4R)-tert-Butyl 2-((1R,2S)-1-(ethoxycarbonyl)-2-vinylcyclopropylcarbamoyl)-4-(4-nitrobenzoyloxy)pyrrolidine-1-carboxylate (2.34 kg) was then added as a solution in EtOAc (8.36 kg) to the acidic ethanol slurry solution at 10° C. The reaction was allowed to proceed for 1 h at 10° C., warmed to 15° C., held at that temperature for 1 h and then warmed to 20° C. After 18 h, EtOAc (8.35 kg) was added to the reactor and the resulting slurry was filtered. The cake was rinsed with EtOAc (8.35 kg) that had been cooled to 0° C. The title compound was placed in a vacuum oven, at 40° C., to remove residual solvent (2.1 kg, 100% yield).

Workup

waitto proceed for 1 h at 10° C.
waitheld at that temperature for 1 h
temperaturewarmed to 20° C
waitAfter 18 h
filtrationthe resulting slurry was filtered
washThe cake was rinsed with EtOAc (8.35 kg) that
temperaturehad been cooled to 0° C
customwas placed in a vacuum oven, at 40° C.

Sources & evidence

ORD record: ord-f5cff39e98bd4ad0ad2d6a2f5a00ea7d
Source dataset: uspto-grants-2014_06
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08748374B2

Linked notes

Loading…