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 1053498Notes

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 617 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 HCL. 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 618 (0.383 g, 72%) as an orange foam.

Workup

temperaturecontinue heating at 170° C. for 3 days

Sources & evidence

ORD record: ord-877ff7ca3bf54892ad0d5db250922637
Source dataset: uspto-grants-2016_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09393256B2

Reaction notes

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