Potassium Carbonate → (1S,4S)-tert-butyl 5-(3-(2-(isopropylamino)-2-oxoethylcarbamoyl)-4-nitrophenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate

HRID 77372Notes

Reaction equation

F[C:2]1[CH:3]=[CH:4][C:5]([N+:18]([O-:20])=[O:19])=[C:6]([CH:17]=1)[C:7]([NH:9][CH2:10][C:11]([NH:13][CH:14]([CH3:16])[CH3:15])=[O:12])=[O:8].C(=O)([O-])[O-].[K+].[K+].[C@H:27]12[CH2:33][C@H:30]([NH:31][CH2:32]1)[CH2:29][N:28]2[C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35]>C(#N)C>[CH:14]([NH:13][C:11](=[O:12])[CH2:10][NH:9][C:7]([C:6]1[CH:17]=[C:2]([N:31]2[CH2:32][C@@H:27]3[CH2:33][C@H:30]2[CH2:29][N:28]3[C:34]([O:36][C:37]([CH3:40])([CH3:39])[CH3:38])=[O:35])[CH:3]=[CH:4][C:5]=1[N+:18]([O-:20])=[O:19])=[O:8])([CH3:16])[CH3:15]

Participants

Conditions

Temperature: 90 °C

Procedure

To a solution of 5-fluoro-N-(2-(isopropylamino)-2-oxoethyl)-2-nitrobenzamide (1.0 g, 3.53 mmol) (Intermediate 2A) in acetonitrile (20 mL) was added potassium carbonate (1.46 g, 10.9 mmol) followed by (1S,4S)-tert-butyl 2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (0.70 g, 3.53 mmol). The resulting suspension was heated to reflux at 90° C. for 6 hours. The reaction mixture was allowed to cool to room temperature, then filtered and concentrated. The resultant crude material was purified by a 25 g silica column in neat ethylacetate (Biotage Snap cartridge). Fractions of the product were combined and reduced to dryness under reduced pressure to afford (1S,4S)-tert-butyl 5-(3-(2-(isopropylamino)-2-oxoethylcarbamoyl)-4-nitrophenyl)-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate (1.5 g, 3.25 mmol).

Workup

temperatureThe resulting suspension was heated
temperatureto cool to room temperature
filtrationfiltered
concentrationconcentrated
customThe resultant crude material was purified by a 25 g silica column in neat ethylacetate (Biotage Snap cartridge)

Sources & evidence

ORD record: ord-6f77caf5ce0344ccb25c3de7609b4efb
Source dataset: uspto-grants-2014_09
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08841289B2

Reaction notes

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