Trifluoroacetic acid → 3-(8-Benzyl-8-aza-bicyclo[3.2.1]oct-2-en-3-yl)-2-hydroxy-benzamide

HRID 1497955Notes

Reaction equation

FC(F)(F)C(O)=[O:4].[CH2:8]([N:15]1[CH:20]2[CH2:21][CH2:22][CH:16]1[CH:17]=[C:18]([C:23]1[C:24]([O:31]C(C)(C)C)=[C:25]([CH:28]=[CH:29][CH:30]=1)[C:26]#[N:27])[CH2:19]2)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1>S(=O)(=O)(O)O>[CH2:8]([N:15]1[CH:20]2[CH2:21][CH2:22][CH:16]1[CH:17]=[C:18]([C:23]1[C:24]([OH:31])=[C:25]([CH:28]=[CH:29][CH:30]=1)[C:26]([NH2:27])=[O:4])[CH2:19]2)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1

Participants

Conditions

Temperature: 65 °C

Procedure

Trifluoroacetic Acid (50 mL) and sulfuric acid (20 mL) were added to crude 3-(8-benzyl-8-aza-bicyclo[3.2.1]oct-2-en-3-yl)-2-tert-butoxy-benzonitrile (37.53 g, 0.101 mol) and the reaction mixture was heated at 65° C. overnight, poured into ice water and neutralized to pH 7. The aqueous layer was extracted EtOAc (3×) and the solvent was evaporated. The reaction mixture was purified by silica gel chromatography (10 min 7% MeOH:DCM, 10 min 10% MeOH:DCM, ramping to 20% MeOH:DCM over 30 min) to provide the title compound (22.15 g). (m/z): [M+H]+ calcd for C21H22N2O2 335.17. found 335.4.

Workup

extractionThe aqueous layer was extracted EtOAc (3×)
customthe solvent was evaporated
customThe reaction mixture was purified by silica gel chromatography (10 min 7% MeOH:DCM, 10 min 10% MeOH:DCM, ramping to 20% MeOH:DCM over 30 min)

Sources & evidence

ORD record: ord-473a7d692a36447390949876aafa7d84
Source dataset: uspto-grants-2015_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09199993B2

Reaction notes

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