tert-Butyl 5-bromoisoindoline-2-carboxylate

Uses

tert-Butyl 5-Bromoisoindoline-2-carboxylate is an intermediate used in the synthesis of Isothiazoloquinolones with Enhanced Antistaphylococcal Activities against Multidrug-Resistant Strains. It is also used to prepare substituted isoindolines as inhibitors of dipeptidyl peptidase 8/9 (DPP8/9).

Synthesis

General procedure for the synthesis of tert-butyl 5-bromoisoindoline-2-carbonate from di-tert-butyl dicarbonate and 5-bromoisoindoline: to a solution of 5-bromoisoindoline (6 g, 30 mmol) in tetrahydrofuran (THF, 100 mL) was added a saturated sodium carbonate solution (25 mL), followed by di-tert-butyl dicarbonate (33 g, 151 mmol). The reaction mixture was stirred at room temperature for 2 hours, followed by concentration under reduced pressure. The residue was extracted with ethyl acetate (50 mL x 3). The organic phases were combined, washed with saturated saline, dried over anhydrous sodium sulfate and concentrated again under reduced pressure. The residue was purified by silica gel column chromatography (petroleum ether: ethyl acetate = 10:1, v/v) to afford the target product tert-butyl 5-bromoisoindoline-2-carboxylate (9 g, approx. 100% yield). lc-MS: 298 [M+1].

References

[1] Patent: US2017/275301, 2017, A1. Location in patent: Paragraph 0226; 0228
[2] Patent: EP3257857, 2017, A1. Location in patent: Paragraph 0102; 0104
[3] Journal of Organic Chemistry, 2012, vol. 77, # 24, p. 11296 - 11301
[4] Patent: WO2015/54317, 2015, A1. Location in patent: Paragraph 0272; 0273
[5] Patent: EP2311810, 2011, A1. Location in patent: Page/Page column 24