N-Boc-L-trans-4,5-Methanoproline

Uses

N-Boc-L-trans-4,5-Methanoproline belongs to carboxylic acid derivatives and can be used as pharmaceutical intermediates.

Uses

1R,3S,5R)-2-(tert-Butoxycarbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxylic Acid acts as a reagent in the preparation of fused bicycles end-capped with peptide derivatives as HCV inhibitors. Synthesis of (tert-butoxycarbonyl)azabicyclohexanecarboxylic acid via stereoselective cyclopropanation of pyrroline

Synthesis

Tert-butyl (1R,3S,5R)-3-(hydroxymethyl)-2-azabicyclo[3.1.0]hexane-2-carboxylate (900 mg, 4.22 mmol, 1.00 eq.) was used as a feedstock and dissolved in a mixed solvent of acetonitrile (10 mL) and carbon tetrachloride (10 mL). To this solution was added an aqueous (10 mL) solution of sodium periodate (2.72 g, 12.72 mmol, 3.00 equiv) and ruthenium trichloride hydrate (44 mg, 0.20 mmol). The reaction mixture was stirred overnight at room temperature. After completion of the reaction, the reaction mixture was diluted with water and extracted with ethyl acetate. The organic phase was washed with brine, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The target product (1R,3S,5R)-2-(tert-butoxycarbonyl)-2-azabicyclo[3.1.0]hexane-3-carboxylic acid (620 mg, 65% yield) was obtained as a brown solid.

References

[1] Angewandte Chemie (International Edition in English), 1997, vol. 36, # 17, p. 1881 - 1884
[2] Patent: WO2015/52264, 2015, A1. Location in patent: Paragraph 01524; 01525
[3] Patent: WO2012/18325, 2012, A1. Location in patent: Page/Page column 145
[4] Patent: WO2012/48421, 2012, A1. Location in patent: Page/Page column 26; 29
[5] Angewandte Chemie - International Edition, 2015, vol. 54, # 45, p. 13268 - 13272