Lithium Hydroxide → 2-(3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-(phosphonomethyl)phenylsulfonamido)acetic acid

Participants

Reaction Steps

Into a 50-mL round-bottom flask, was placed a solution of (3-(6,8-dichloro-2-methyl-1,2,3,4-tetrahydroisoquinolin-4-yl)-N-(2-ethoxy-2-oxoethyl)phenylsulfonamido)methylphosphonic acid (Intermediate 8.4) (180 mg, 0.33 mmol, 1.00 equiv) in tetrahydrofuran/water (5/5 mL). This was followed by the addition of lithium hydroxide (39 mg, 1.62 mmol, 4.97 equiv) in several batches at room temperature. The resulting solution was stirred for 4 h at room temperature. The reaction progress was monitored by LCMS. The resulting mixture was concentrated under vacuum. The pH value of the solution was adjusted to 6 with 1M hydrogen chloride. The resulting mixture was concentrated under vacuum. The crude product (150 mg) was purified by preparative HPLC giving 59.2 mg (35%) of the title compound as a TFA salt. 1H-NMR (300 MHz, DMSO+D2O, ppm): 7.73˜7.74 (m, 1H), 7.67˜7.68 (m, 1H), 7.58˜7.62 (m, 2H), 7.49 (s, 1H), 7.00 (s, 1H), 4.71˜4.75 (m, 1H), 4.49 (d, J=16.2 Hz, 1H), 4.33 (d, J=15.9 Hz, 1H), 4.07 (s, 2H), 3.62˜3.64 (m, 1H), 3.45˜3.54 (m, 2H), 3.31˜3.40 (m, 1H), 2.88 (s, 3H). MS (ES, m/z): 523 [M+H]+.

Provenance & Evidence