3-(2-Amino-4-bromo-phenylcarbamoyl)-2-azabicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester → 3-(6-Bromo-1H-benzoimidazol-2-yl)-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester

HRID 2039103Notes

Reaction equation

[C:1]([O:5][C:6]([N:8]1[CH:13]([C:14](=O)[NH:15][C:16]2[CH:21]=[CH:20][C:19]([Br:22])=[CH:18][C:17]=2[NH2:23])[CH:12]2[CH2:25][CH:9]1[CH2:10][CH2:11]2)=[O:7])([CH3:4])([CH3:3])[CH3:2]>C(O)C>[C:1]([O:5][C:6]([N:8]1[CH:13]([C:14]2[NH:23][C:17]3[CH:18]=[C:19]([Br:22])[CH:20]=[CH:21][C:16]=3[N:15]=2)[CH:12]2[CH2:25][CH:9]1[CH2:10][CH2:11]2)=[O:7])([CH3:4])([CH3:3])[CH3:2]

Participants

Conditions

Temperature: 130 °C

Procedure

The above mixture of regioisomer 3-(2-Amino-4-bromo-phenylcarbamoyl)-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester was dissolved in ethanol and heated to 130° C. in sealed tube overnight and continue heating at 170° C. for 3 days. LC-MS showed desired product and Boc cleaved product (about 1:1 ratio). The mixture was concentrated down and dissolved DCM. Di-tert-butyl dicarbonate (0.6 eq.) was added and reaction was stirred overnight at room temperature. The reaction mixture was concentrated down and purified by flash column chromatography (silica gel, 20 to 80% ethyl acetate/hexane) to give 3-(6-Bromo-1H-benzoimidazol-2-yl)-2-aza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (0.383 g, 72%) as an orange foam.

Workup

temperaturecontinue heating at 170° C. for 3 days

Sources & evidence

ORD record: ord-c8f5dd5c5e75444d9d90dcc8d383e963
Source dataset: uspto-grants-2013_11
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08575118B2

Reaction notes

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