Ammonium formate → tert-Butyl ((1S,5R,6S)-3-azabicyclo[3.3.0]octan-6-yl)carbamate

HRID 2363536Notes

Reaction equation

C([N:8]1[CH2:12][C@@H:11]2[C@@H:13]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:22])([CH3:21])[CH3:20])[CH2:14][CH2:15][C@@H:10]2[CH2:9]1)C1C=CC=CC=1.C([O-])=O.[NH4+]>C(O)C.[Pd]>[CH2:9]1[C@H:10]2[CH2:15][CH2:14][C@H:13]([NH:16][C:17](=[O:23])[O:18][C:19]([CH3:21])([CH3:20])[CH3:22])[C@H:11]2[CH2:12][NH:8]1

Participants

Conditions

Temperature: 90 °C

Procedure

tert-Butyl(3aR,4S,6aS)-2-benzyloctahydrocyclopenta[c]pyrrol-4-ylcarbamate (100 mg, 0.316 mmol) from Step A and ammonium formate (100 mg, 1.580 mmol) were combined in ethanol. The reaction was deoxygenated at low temperature, and palladium on carbon (3.36 mg, 0.032 mmol) was added. The reaction was heated to reflux under nitrogen. After 3 hours, TLC and LCMS showed mostly starting material. Degussa's catalyst and 5 equivalents more ammonium formate were added and the reaction mixture was refluxed under nitrogen overnight. More ammonium formate and Degussa's catalyst were added and the reaction heated to 90° C. After 2 hours, TLC and LCMS showed no remaining starting material. The reaction was filtered through diatomaceous earth containing carbonate functionalized silica gel (Silicycle, Quebec, Canada) with methanol. Solvent removal in vacuo gave tert-butyl(3aR,4S,6aS)-octahydrocyclopenta[c]pyrrol-4-ylcarbamate: MS (ESI+) m/z 226 (M+H)+.

Workup

additionwas added
temperatureThe reaction was heated
temperatureto reflux under nitrogen
temperaturethe reaction mixture was refluxed under nitrogen overnight
waitAfter 2 hours
filtrationThe reaction was filtered through diatomaceous earth
additioncontaining carbonate functionalized silica gel (Silicycle, Quebec, Canada) with methanol
customSolvent removal in vacuo

Sources & evidence

ORD record: ord-8c063cdf8eea4e609539e94717ddaefc
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08691865B2

Reaction notes

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