Water → (2S,4S)-1-[2-[(4-ethoxycarbonylbicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carboxamide

HRID 1099381Notes

Reaction equation

C(=O)([O-])[O-].[K+].[K+].Cl.[NH2:8][C:9]12[CH2:16][CH2:15][C:12]([C:17]([O:19][CH2:20][CH3:21])=[O:18])([CH2:13][CH2:14]1)[CH2:11][CH2:10]2.[F:22][C@@H:23]1[CH2:27][N:26]([C:28](=[O:40])[CH2:29]OS(C2C=CC=CC=2)(=O)=O)[C@H:25]([C:41]([NH2:43])=[O:42])[CH2:24]1.O>CN(C)C=O>[CH2:20]([O:19][C:17]([C:12]12[CH2:11][CH2:10][C:9]([NH:8][CH2:29][C:28]([N:26]3[CH2:27][C@@H:23]([F:22])[CH2:24][C@H:25]3[C:41]([NH2:43])=[O:42])=[O:40])([CH2:16][CH2:15]1)[CH2:14][CH2:13]2)=[O:18])[CH3:21]

Participants

Conditions

Temperature: 40 °C

Procedure

Potassium carbonate (277 mg) was added to a solution of ethyl 4-aminobicyclo[2.2.2]octane-1-carboxylate hydrochloride (319 mg) in N,N-dimethylformamide (1.8 mL), followed by stirring at an inner temperature of 40° C. for 30 minutes. (2S,4S)-4-Fluoro-1-[2-(benzenesulfonyloxy)acetyl]pyrrolidine-2-carboxamide (295 mg) was added thereto, followed by stirring at the same temperature for 1 hour. Water (5.4 mL) was added to the reaction solution, followed by stirring at an inner temperature of from 5 to 10° C. for 30 minutes. The precipitate were collected by filtration, washed with cold water (4 mL) and then blast-dried at an outer temperature of 40° C., thereby obtaining white crystals of (2S,4S)-1-[2-[(4-ethoxycarbonylbicyclo[2.2.2]oct-1-yl)amino]acetyl]-4-fluoropyrrolidine-2-carboxamide (obtained amount: 247 mg, yield: 75%).

Workup

stirringby stirring at the same temperature for 1 hour
stirringby stirring at an inner temperature of from 5 to 10° C. for 30 minutes
filtrationThe precipitate were collected by filtration
washwashed with cold water (4 mL)
customblast-dried at an outer temperature of 40° C.

Sources & evidence

ORD record: ord-a5aae870c8ad4e039b71ce290057675f
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08143427B2

Reaction notes

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