2-(tert-Butoxycarbonyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxylic acid

Uses

2-BOC-7-carboxy-1,2,3,4-tetrahydroisoquinoline is a quinoline derivative used in pharmaceutical synthesis and experimental research.

Synthesis

2-tert-butyl 7-methyl 3,4-dihydroisoquinoline-2,7(1H)-dicarboxylate (450 mg, 1.545 mmol) was used as a raw material and dissolved in tetrahydrofuran (THF, 2 mL) and methanol (MeOH, 1 mL). Lithium hydroxide (LiOH, 111 mg, 4.63 mmol) and water (H2O, 1 mL) were added. The reaction mixture was heated to 60 °C and stirred at this temperature for 3 hours. Upon completion of the reaction, the solvent was evaporated until the remaining predominantly aqueous layer. The aqueous layer was cooled in an ice bath and adjusted to slightly acidic by slowly adding 5 M hydrochloric acid (HCl) dropwise. Extraction was performed with ethyl acetate (EtOAc, 10 mL) and water (H2O, 10 mL). The aqueous layer was again extracted with ethyl acetate (10 mL). The organic layers were combined, dried and concentrated to give a colorless oil, which was solidified overnight under reduced pressure. The resulting solid precipitate was ground in methyl tert-butyl ether (MTBE), filtered and dried to afford 2-(tert-butoxycarbonyl)-1,2,3,4-tetrahydroisoquinoline-7-carboxylic acid (260 mg, 58.3% yield).LC/MS m/z = 278.2 [M + H]+; 1H NMR (400 MHz, DMSO-d6) δ ppm 1.43 (s , 9H), 2.83 (t, J = 5.87 Hz, 2H), 3.56 (t, J = 5.94 Hz, 2H), 4.55 (s, 2H), 7.28 (d, J = 7.96 Hz, 1H), 7.70-7.75 (m, 2H), 12.84 (br s, 1H).

References

[1] Patent: WO2013/70657, 2013, A1. Location in patent: Page/Page column 153; 175
[2] Patent: US2010/234340, 2010, A1. Location in patent: Page/Page column 63